Pancreatic cancer stem cell markers and exosomes- the incentive push
|
摘要
Pancreatic cancer(Pa Ca) has the highest death rate and incidence is increasing. Poor prognosis is due to late diagnosis and early metastatic spread, which is ascribed to a minor population of so called cancer stem cells(CSC) within the mass of the primary tumor. CSC are defined by biological features, which they share with adult stem cells like longevity, rare cell division, the capacity for self renewal, differentiation, drug resistance and the requirement for a niche. CSC can also be identified by sets of markers, which for pancreatic CSC(Pa-CSC) include CD44v6, c-Met, Tspan8, alpha6beta4, CXCR4, CD133, Ep CAM and claudin7. The functional relevance of CSC markers is still disputed. We hypothesize that Pa-CSC markers play a decisive role in tumor progression. This is fostered by the location in glycolipid-enriched membrane domains, which function as signaling platform and support connectivity of the individual Pa-CSC markers. Outsidein signaling supports apoptosis resistance, stem cell gene expression and tumor suppressor gene repression as well as mi RNA transcription and silencing. Pa-CSC markers also contribute to motility and invasiveness. By ligand binding host cells are triggered towards creating a milieu supporting Pa-CSC maintenance. Furthermore, CSC markers contribute to the generation, loading and delivery of exosomes, whereby CSC gain the capacity for a cell-cell contact independent crosstalk with the host and neighboring non-CSC. This allows PaCSC exosomes(TEX) to reprogram neighboring nonCSC towards epithelial mesenchymal transition and to stimulate host cells towards preparing a niche for metastasizing tumor cells. Finally, TEX communicate with the matrix to support tumor cell motility, invasion and homing. We will discuss the possibility that CSC markers are the initial trigger for these processes and what is the special contribution of CSC-TEX.
Pancreatic cancer(Pa Ca) has the highest death rate and incidence is increasing. Poor prognosis is due to late diagnosis and early metastatic spread, which is ascribed to a minor population of so called cancer stem cells(CSC) within the mass of the primary tumor. CSC are defined by biological features, which they share with adult stem cells like longevity, rare cell division, the capacity for self renewal, differentiation, drug resistance and the requirement for a niche. CSC can also be identified by sets of markers, which for pancreatic CSC(Pa-CSC) include CD44v6, c-Met, Tspan8, alpha6beta4, CXCR4, CD133, Ep CAM and claudin7. The functional relevance of CSC markers is still disputed. We hypothesize that Pa-CSC markers play a decisive role in tumor progression. This is fostered by the location in glycolipid-enriched membrane domains, which function as signaling platform and support connectivity of the individual Pa-CSC markers. Outsidein signaling supports apoptosis resistance, stem cell gene expression and tumor suppressor gene repression as well as mi RNA transcription and silencing. Pa-CSC markers also contribute to motility and invasiveness. By ligand binding host cells are triggered towards creating a milieu supporting Pa-CSC maintenance. Furthermore, CSC markers contribute to the generation, loading and delivery of exosomes, whereby CSC gain the capacity for a cell-cell contact independent crosstalk with the host and neighboring non-CSC. This allows PaCSC exosomes(TEX) to reprogram neighboring nonCSC towards epithelial mesenchymal transition and to stimulate host cells towards preparing a niche for metastasizing tumor cells. Finally, TEX communicate with the matrix to support tumor cell motility, invasion and homing. We will discuss the possibility that CSC markers are the initial trigger for these processes and what is the special contribution of CSC-TEX.
Pancreatic cancer(Pa Ca) has the highest death rate and incidence is increasing. Poor prognosis is due to late diagnosis and early metastatic spread, which is ascribed to a minor population of so called cancer stem cells(CSC) within the mass of the primary tumor. CSC are defined by biological features, which they share with adult stem cells like longevity, rare cell division, the capacity for self renewal, differentiation, drug resistance and the requirement for a niche. CSC can also be identified by sets of markers, which for pancreatic CSC(Pa-CSC) include CD44v6, c-Met, Tspan8, alpha6beta4, CXCR4, CD133, Ep CAM and claudin7. The functional relevance of CSC markers is still disputed. We hypothesize that Pa-CSC markers play a decisive role in tumor progression. This is fostered by the location in glycolipid-enriched membrane domains, which function as signaling platform and support connectivity of the individual Pa-CSC markers. Outsidein signaling supports apoptosis resistance, stem cell gene expression and tumor suppressor gene repression as well as mi RNA transcription and silencing. Pa-CSC markers also contribute to motility and invasiveness. By ligand binding host cells are triggered towards creating a milieu supporting Pa-CSC maintenance. Furthermore, CSC markers contribute to the generation, loading and delivery of exosomes, whereby CSC gain the capacity for a cell-cell contact independent crosstalk with the host and neighboring non-CSC. This allows PaCSC exosomes(TEX) to reprogram neighboring nonCSC towards epithelial mesenchymal transition and to stimulate host cells towards preparing a niche for metastasizing tumor cells. Finally, TEX communicate with the matrix to support tumor cell motility, invasion and homing. We will discuss the possibility that CSC markers are the initial trigger for these processes and what is the special contribution of CSC-TEX.
引文
1 Siegel R,Naishadham D,Jemal A.Cancer statistics,2013.CA Cancer J Clin 2013;63:11-30[PMID:23335087 DOI:10.3322/caac.21166]
2 Wang Z,Lai ST,Xie L,Zhao JD,Ma NY,Zhu J,Ren ZG,Jiang GL.Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus:a systematic review and meta-analysis.Diabetes Res Clin Pract 2014;106:19-26[PMID:24837144 DOI:10.1016/j.diabres.2014.04.007]
3 Wang XY,Yang F,Jin C,Fu DL.Utility of PET/CT in diagnosis,staging,assessment of resectability and metabolic response of pancreatic cancer.World J Gastroenterol 2014;20:15580-15589[PMID:25400441 DOI:10.3748/wjg.v20.i42.15580]
4 Urayama S.Pancreatic cancer early detection:expanding higherrisk group with clinical and metabolomics parameters.World J Gastroenterol 2015;21:1707-1717[PMID:25684935 DOI:10 .3748/wjg.v21.i6.1707]
5 Del Chiaro M,Segersv?rd R,Lohr M,Verbeke C.Early detection and prevention of pancreatic cancer:is it really possible today?World J Gastroenterol 2014;20:12118-12131[PMID:25232247DOI:10.3748/wjg.v20.i34.12118]
6 Jenkinson C,Earl J,Ghaneh P,Halloran C,Carrato A,Greenhalf W,Neoptolemos J,Costello E.Biomarkers for early diagnosis of pancreatic cancer.Expert Rev Gastroenterol Hepatol 2015;9:305-315[PMID:25373768 DOI:10.1586/17474124.2015.965145]
7 Ansari D,Gustafsson A,Andersson R.Update on the management of pancreatic cancer:surgery is not enough.World J Gastroenterol2015;21:3157-3165[PMID:25805920 DOI:10.3748/wjg.v21.i11.3157]
8 Okano K,Suzuki Y.Strategies for early detection of resectable pancreatic cancer.World J Gastroenterol 2014;20:11230-11240[PMID:25170207 DOI:10.3748/wjg.v20.i32.11230]
9 He XY,Yuan YZ.Advances in pancreatic cancer research:moving towards early detection.World J Gastroenterol 2014;20:11241-11248[PMID:25170208 DOI:10.3748/wjg.v20.i32.11241]
10 Goonetilleke KS,Siriwardena AK.Systematic review of carbohydrate antigen(CA 19-9)as a biochemical marker in the diagnosis of pancreatic cancer.Eur J Surg Oncol 2007;33:266-270[PMID:17097848]
11 Bussom S,Saif MW.Methods and rationale for the early detection of pancreatic cancer.Highlights from the“2010 ASCO Gastrointestinal Cancers Symposium”.Orlando,FL,USA.January22 -24,2010.JOP 2010;11:128-130[PMID:20208319]
12 Gold DV,Modrak DE,Ying Z,Cardillo TM,Sharkey RM,Goldenberg DM.New MUC1 serum immunoassay differentiates pancreatic cancer from pancreatitis.J Clin Oncol 2006;24:252-258[PMID:16344318]
13 Canto MI,Goggins M,Yeo CJ,Griffin C,Axilbund JE,Brune K,Ali SZ,Jagannath S,Petersen GM,Fishman EK,Piantadosi S,Giardiello FM,Hruban RH.Screening for pancreatic neoplasia in high-risk individuals:an EUS-based approach.Clin Gastroenterol Hepatol 2004;2:606-621[PMID:15224285]
14 Chen Y,Kang M,Lu W,Guo Q,Zhang B,Xie Q,Wu Y.DJ-1,a novel biomarker and a selected target gene for overcoming chemoresistance in pancreatic cancer.J Cancer Res Clin Oncol 2012;138:1463-1474[PMID:22526154 DOI:10.1007/s00432-012-1205-3]
15 Makawita S,Dimitromanolakis A,Soosaipillai A,Soleas I,Chan A,Gallinger S,Haun RS,Blasutig IM,Diamandis EP.Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9.BMC Cancer 2013;13:404[PMID:24007603 DOI:10.1186/1471-2407-13-404]
16 Wingren C,Sandstr?m A,Segersv?rd R,Carlsson A,Andersson R,L?hr M,Borrebaeck CA.Identification of serum biomarker signatures associated with pancreatic cancer.Cancer Res 2012;72:2481-2490[PMID:22589272 DOI:10.1158/0008-5472.CAN-11-2883]
17 Ansari D,Andersson R,Bauden MP,Andersson B,Connolly JB,Welinder C,Sasor A,Marko-Varga G.Protein deep sequencing applied to biobank samples from patients with pancreatic cancer.J Cancer Res Clin Oncol 2015;141:369-380[PMID:25216700DOI:10.1007/s00432-014-1817-x]
18 Chen R,Yi EC,Donohoe S,Pan S,Eng J,Cooke K,Crispin DA,Lane Z,Goodlett DR,Bronner MP,Aebersold R,Brentnall TA.Pancreatic cancer proteome:the proteins that underlie invasion,metastasis,and immunologic escape.Gastroenterology 2005;129:1187-1197[PMID:16230073]
19 Lu Z,Hu L,Evers S,Chen J,Shen Y.Differential expression profiling of human pancreatic adenocarcinoma and healthy pancreatic tissue.Proteomics 2004;4:3975-3988[PMID:15526344]
20 Shen J,Person MD,Zhu J,Abbruzzese JL,Li D.Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry.Cancer Res 2004;64:9018-9026[PMID:15604267]
21 Fukushige S,Horii A.Road to early detection of pancreatic cancer:Attempts to utilize epigenetic biomarkers.Cancer Lett 2014;342:231-237[PMID:22450751 DOI:10.1016/j.canlet.2012.03.022]
22 Rachagani S,Macha MA,Heimann N,Seshacharyulu P,Haridas D,Chugh S,Batra SK.Clinical implications of mi RNAs in the pathogenesis,diagnosis and therapy of pancreatic cancer.Adv Drug Deliv Rev 2015;81:16-33[PMID:25453266 DOI:10.1016/j.addr.2014.10.020]
23 Z?ller M.Pancreatic cancer diagnosis by free and exosomal mi RNA.World J Gastrointest Pathophysiol 2013;4:74-90[PMID:24340225 DOI:10.4291/wjgp.v4.i4.74]
24 Yi JM,Guzzetta AA,Bailey VJ,Downing SR,Van Neste L,Chiappinelli KB,Keeley BP,Stark A,Herrera A,Wolfgang C,Pappou EP,Iacobuzio-Donahue CA,Goggins MG,Herman JG,Wang TH,Baylin SB,Ahuja N.Novel methylation biomarker panel for the early detection of pancreatic cancer.Clin Cancer Res2013;19:6544-6555[PMID:24088737 DOI:10.1158/1078-0432.CCR-12-3224]
25 Nagpal G,Sharma M,Kumar S,Chaudhary K,Gupta S,Gautam A,Raghava GP.PCMdb:pancreatic cancer methylation database.Sci Rep 2014;4:4197[PMID:24569397 DOI:10.1038/srep04197]
26 Jin K,Luo G,Xiao Z,Liu Z,Liu C,Ji S,Xu J,Liu L,Long J,Ni Q,Yu X.Noncoding RNAs as potential biomarkers to predict the outcome in pancreatic cancer.Drug Des Devel Ther 2015;9:1247-1255[PMID:25750521 DOI:10.2147/DDDT.S77597]
27 Wang J,Chen J,Chang P,Le Blanc A,Li D,Abbruzzesse JL,Frazier ML,Killary AM,Sen S.Micro RNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease.Cancer Prev Res(Phila)2009;2:807-813[PMID:19723895 DOI:10.1158/1940-6207.CAPR-09-0094]
28 Liu J,Gao J,Du Y,Li Z,Ren Y,Gu J,Wang X,Gong Y,Wang W,Kong X.Combination of plasma micro RNAs with serum CA19-9for early detection of pancreatic cancer.Int J Cancer 2012;131:683-691[PMID:21913185 DOI:10.1002/ijc.26422]
29 Liu R,Chen X,Du Y,Yao W,Shen L,Wang C,Hu Z,Zhuang R,Ning G,Zhang C,Yuan Y,Li Z,Zen K,Ba Y,Zhang CY.Serum micro RNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer.Clin Chem 2012;58:610-618[PMID:22194634 DOI:10.1373/clinchem.2011.172767]
30 Schultz NA,Dehlendorff C,Jensen BV,Bjerregaard JK,Nielsen KR,Bojesen SE,Calatayud D,Nielsen SE,Yilmaz M,Holl?nder NH,Andersen KK,Johansen JS.Micro RNA biomarkers in whole blood for detection of pancreatic cancer.JAMA 2014;311:392-404[PMID:24449318 DOI:10.1001/jama.2013.284664]
31 Wan C,Shen Y,Yang T,Wang T,Chen L,Wen F.Diagnostic value of micro RNA for pancreatic cancer:a meta-analysis.Arch Med Sci 2012;8:749-755[PMID:23185182 DOI:10.5114/aoms.2012.31609]
32 Kahlert C,Melo SA,Protopopov A,Tang J,Seth S,Koch M,Zhang J,Weitz J,Chin L,Futreal A,Kalluri R.Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.J Biol Chem 2014;289:3869-3875[PMID:24398677 DOI:10.1074/jbc.C113.532267]
33 Que R,Ding G,Chen J,Cao L.Analysis of serum exosomal micro RNAs and clinicopathologic features of patients with pancreatic adenocarcinoma.World J Surg Oncol 2013;11:219[PMID:24007214 DOI:10.1186/1477-7819-11-219]
34 Melo SA,Luecke LB,Kahlert C,Fernandez AF,Gammon ST,Kaye J,Le Bleu VS,Mittendorf EA,Weitz J,Rahbari N,Reissfelder C,Pilarsky C,Fraga MF,Piwnica-Worms D,Kalluri R.Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.Nature 2015;523:177-182[PMID:26106858 DOI:10 .1038/nature14581]
35 Madhavan B,Yue S,Galli U,Rana S,Gross W,Müller M,Giese NA,Kalthoff H,Becker T,Büchler MW,Z?ller M.Combined evaluation of a panel of protein and mi RNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity.Int J Cancer 2015;136:2616-2627[PMID:25388097 DOI:10.1002/ijc.29324]
36 Sohal DP,Walsh RM,Ramanathan RK,Khorana AA.Pancreatic adenocarcinoma:treating a systemic disease with systemic therapy.J Natl Cancer Inst 2014;106:dju011[PMID:24563516 DOI:10 .1093/jnci/dju011]
37 Greenow K,Clarke AR.Controlling the stem cell compartment and regeneration in vivo:the role of pluripotency pathways.Physiol Rev 2012;92:75-99[PMID:22298652 DOI:10.1152/physrev.00040.2010]
38 Sales KM,Winslet MC,Seifalian AM.Stem cells and cancer:an overview.Stem Cell Rev 2007;3:249-255[PMID:17955391]
39 Ta m W L,Weinberg RA.The epigenetics of epithelialmesenchymal plasticity in cancer.Nat Med 2013;19:1438-1449[PMID:24202396 DOI:10.1038/nm.3336]
40 Cerdan C,Bhatia M.Novel roles for Notch,Wnt and Hedgehog in hematopoesis derived from human pluripotent stem cells.Int J Dev Biol 2010;54:955-963[PMID:20336604 DOI:10.1387/ijdb.103067cc]
41 Fossett N.Signal transduction pathways,intrinsic regulators,and the control of cell fate choice.Biochim Biophys Acta 2013;1830:2375-2384[PMID:22705942 DOI:10.1016/j.bbagen.2012.06.005]
42 Brabletz T,Jung A,Spaderna S,Hlubek F,Kirchner T.Opinion:migrating cancer stem cells-an integrated concept of malignant tumour progression.Nat Rev Cancer 2005;5:744-749[PMID:16148886]
43 Thiery JP,Acloque H,Huang RY,Nieto MA.Epithelialmesenchymal transitions in development and disease.Cell 2009;139:871-890[PMID:19945376 DOI:10.1016/j.cell.2009.11.007]
44 Mani SA,Guo W,Liao MJ,Eaton EN,Ayyanan A,Zhou AY,Brooks M,Reinhard F,Zhang CC,Shipitsin M,Campbell LL,Polyak K,Brisken C,Yang J,Weinberg RA.The epithelialmesenchymal transition generates cells with properties of stem cells.Cell 2008;133:704-715[PMID:18485877 DOI:10.1016/j.cell.2008.03.027]
45 Wang Z,Ali S,Banerjee S,Bao B,Li Y,Azmi AS,Korc M,Sarkar FH.Activated K-Ras and INK4a/Arf deficiency promote aggressiveness of pancreatic cancer by induction of EMT consistent with cancer stem cell phenotype.J Cell Physiol 2013;228:556-562[PMID:22806240 DOI:10.1002/jcp.24162]
46 Biddle A,Mackenzie IC.Cancer stem cells and EMT in carcinoma.Cancer Metastasis Rev 2012;Epub ahead of print[PMID:22302111]
47 Scheel C,Eaton EN,Li SH,Chaffer CL,Reinhardt F,Kah KJ,Bell G,Guo W,Rubin J,Richardson AL,Weinberg RA.Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast.Cell 2011;145:926-940[PMID:21663795DOI:10.1016/j.cell.2011.04.029]
48 Lamouille S,Xu J,Derynck R.Molecular mechanisms of epithelial-mesenchymal transition.Nat Rev Mol Cell Biol 2014;15:178-196[PMID:24556840 DOI:10.1038/nrm3758]
49 Tania M,Khan MA,Fu J.Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer.Tumour Biol2014;35:7335-7342[PMID:24880591 DOI:10.1007/s13277-014 -2163-y]
50 Moustakas A,Heldin P.TGFβand matrix-regulated epithelial to mesenchymal transition.Biochim Biophys Acta 2014;1840:2621-2634[PMID:24561266 DOI:10.1016/j.bbagen.2014.02.004]
51 Taylor MA,Parvani JG,Schiemann WP.The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-beta in normal and malignant mammary epithelial cells.J Mammary Gland Biol Neoplasia 2010;15:169-190[PMID:20467795 DOI:10.1007/s10911-010-9181-1]
52 Reya T,Clevers H.Wnt signalling in stem cells and cancer.Nature2005;434:843-850[PMID:15829953]
53 Vermeulen L,De Sousa E Melo F,van der Heijden M,Cameron K,de Jong JH,Borovski T,Tuynman JB,Todaro M,Merz C,Rodermond H,Sprick MR,Kemper K,Richel DJ,Stassi G,Medema JP.Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.Nat Cell Biol 2010;12:468-476[PMID:20418870 DOI:10.1038/ncb2048]
54 Yook JI,Li XY,Ota I,Hu C,Kim HS,Kim NH,Cha SY,Ryu JK,Choi YJ,Kim J,Fearon ER,Weiss SJ.A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells.Nat Cell Biol 2006;8:1398-1406[PMID:17072303]
55 Brabletz S,Bajdak K,Meidhof S,Burk U,Niedermann G,Firat E,Wellner U,Dimmler A,Faller G,Schubert J,Brabletz T.The ZEB1/mi R-200 feedback loop controls Notch signalling in cancer cells.EMBO J 2011;30:770-782[PMID:21224848 DOI:10 .1038/emboj.2010.349]
56 Thomson S,Petti F,Sujka-Kwok I,Mercado P,Bean J,Monaghan M,Seymour SL,Argast GM,Epstein DM,Haley JD.A systems view of epithelial-mesenchymal transition signaling states.Clin Exp Metastasis 2011;28:137-155[PMID:21194007 DOI:10 .1007/s10585-010-9367-3]
57 Hardy KM,Booth BW,Hendrix MJ,Salomon DS,Strizzi L.Erb B/EGF signaling and EMT in mammary development and breast cancer.J Mammary Gland Biol Neoplasia 2010;15:191-199[PMID:20369376 DOI:10.1007/s10911-010-9172-2]
58 Peinado H,Olmeda D,Cano A.Snail,Zeb and b HLH factors in tumour progression:an alliance against the epithelial phenotype?Nat Rev Cancer 2007;7:415-428[PMID:17508028]
59 Cedar H,Bergman Y.Linking DNA methylation and histone modification:patterns and paradigms.Nat Rev Genet 2009;10:295-304[PMID:19308066 DOI:10.1038/nrg2540]
60 Song LB,Li J,Liao WT,Feng Y,Yu CP,Hu LJ,Kong QL,Xu LH,Zhang X,Liu WL,Li MZ,Zhang L,Kang TB,Fu LW,Huang WL,Xia YF,Tsao SW,Li M,Band V,Band H,Shi QH,Zeng YX,Zeng MS.The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells.J Clin Invest 2009;119:3626-3636[PMID:19884659 DOI:10.1172/JCI39374]
61 Martin A,Cano A.Tumorigenesis:Twist1 links EMT to selfrenewal.Nat Cell Biol 2010;12:924-925[PMID:20885418 DOI:10 .1038/ncb1010-924]
62 von Burstin J,Eser S,Paul MC,Seidler B,Brandl M,Messer M,von Werder A,Schmidt A,Mages J,Pagel P,Schnieke A,Schmid RM,Schneider G,Saur D.E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex.Gastroenterology 2009;137:361-71,371 .e1-5[PMID:19362090 DOI:10.1053/j.gastro.2009.04.004]
63 Fu J,Qin L,He T,Qin J,Hong J,Wong J,Liao L,Xu J.The TWIST/Mi2/Nu RD protein complex and its essential role in cancer metastasis.Cell Res 2011;21:275-289[PMID:20714342 DOI:10 .1038/cr.2010.118]
64 Scherr M,Eder M.Gene silencing by small regulatory RNAs in mammalian cells.Cell Cycle 2007;6:444-449[PMID:17312397]
65 Gregory PA,Bert AG,Paterson EL,Barry SC,Tsykin A,Farshid G,Vadas MA,Khew-Goodall Y,Goodall GJ.The mi R-200 family and mi R-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.Nat Cell Biol 2008;10:593-601[PMID:18376396 DOI:10.1038/ncb1722]
66 Ru P,Steele R,Newhall P,Phillips NJ,Toth K,Ray RB.mi RNA-29 b suppresses prostate cancer metastasis by regulating epithelialmesenchymal transition signaling.Mol Cancer Ther 2012;11:1166-1173[PMID:22402125 DOI:10.1158/1535-7163.MCT-12-0100]
67 Zhang J,Zhang H,Liu J,Tu X,Zang Y,Zhu J,Chen J,Dong L,Zhang J.mi R-30 inhibits TGF-β1-induced epithelial-tomesenchymal transition in hepatocyte by targeting Snail1.Biochem Biophys Res Commun 2012;417:1100-1105[PMID:22227196DOI:10.1016/j.bbrc.2011.12.121]
68 Gandellini P,Giannoni E,Casamichele A,Taddei ML,Callari M,Piovan C,Valdagni R,Pierotti MA,Zaffaroni N,Chiarugi P.mi R-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts.Antioxid Redox Signal 2014;20:1045-1059[PMID:23924028 DOI:10.1089/ars.2013.5292]
69 Ma L,Young J,Prabhala H,Pan E,Mestdagh P,Muth D,TeruyaFeldstein J,Reinhardt F,Onder TT,Valastyan S,Westermann F,Speleman F,Vandesompele J,Weinberg RA.mi R-9,a MYC/MYCN-activated micro RNA,regulates E-cadherin and cancer metastasis.Nat Cell Biol 2010;12:247-256[PMID:20173740DOI:10.1038/ncb2024]
70 Meng Z,Fu X,Chen X,Zeng S,Tian Y,Jove R,Xu R,Huang W.mi R-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice.Hepatology 2010;52:2148-2157[PMID:20979124 DOI:10.1002/hep.23915]
71 Vetter G,Saumet A,Moes M,Vallar L,Le Béchec A,Laurini C,Sabbah M,Arar K,Theillet C,Lecellier CH,Friederich E.mi R-661expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1and Star D10 messengers.Oncogene 2010;29:4436-4448[PMID:20543867 DOI:10.1038/onc.2010.181]
72 Zhou Q,Fan J,Ding X,Peng W,Yu X,Chen Y,Nie J.TGF-{beta}-induced Mi R-491-5p expression promotes Par-3degradation in rat proximal tubular epithelial cells.J Biol Chem2010;285:40019-40027[PMID:20966078 DOI:10.1074/jbc.M110.141341]
73 Hamada S,Satoh K,Miura S,Hirota M,Kanno A,Masamune A,Kikuta K,Kume K,Unno J,Egawa S,Motoi F,Unno M,Shimosegawa T.mi R-197 induces epithelial-mesenchymal transition in pancreatic cancer cells by targeting p120 catenin.J Cell Physiol 2013;228:1255-1263[PMID:23139153 DOI:10 .1002/jcp.24280]
74 Chang CJ,Chao CH,Xia W,Yang JY,Xiong Y,Li CW,Yu WH,Rehman SK,Hsu JL,Lee HH,Liu M,Chen CT,Yu D,Hung MC.p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating mi RNAs.Nat Cell Biol 2011;13:317-323[PMID:21336307 DOI:10.1038/ncb2173]
75 Chen D,Zhang Y,Wang J,Chen J,Yang C,Cai K,Wang X,Shi F,Dou J.Micro RNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ovarian cancer stem cells by regulating epithelial-mesenchymal transition.J Ovarian Res 2013;6:50[PMID:23842108 DOI:10.1186/1757-2215-6-50]
76 Han M,Liu M,Wang Y,Chen X,Xu J,Sun Y,Zhao L,Qu H,Fan Y,Wu C.Antagonism of mi R-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2inactivation by targeting PTEN.PLo S One 2012;7:e39520[PMID:22761812 DOI:10.1371/journal.pone.0039520]
77 Tsai JH,Donaher JL,Murphy DA,Chau S,Yang J.Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis.Cancer Cell 2012;22:725-736[PMID:23201165 DOI:10.1016/j.ccr.2012.09.022]
78 Siemens H,Jackstadt R,Hünten S,Kaller M,Menssen A,G?tz U,Hermeking H.mi R-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions.Cell Cycle 2011;10:4256-4271[PMID:22134354 DOI:10.4161/cc.10.24.18552]
79 Brabletz S,Brabletz T.The ZEB/mi R-200 feedback loop--a motor of cellular plasticity in development and cancer?EMBO Rep 2010;11:670-677[PMID:20706219 DOI:10.1038/embor.2010.117]
80 Moes M,Le Béchec A,Crespo I,Laurini C,Halavatyi A,Vetter G,Del Sol A,Friederich E.A novel network integrating a mi RNA-203/SNAI1 feedback loop which regulates epithelial to mesenchymal transition.PLo S One 2012;7:e35440[PMID:22514743 DOI:10.1371/journal.pone.0035440]
81 Fuchs E,Tumbar T,Guasch G.Socializing with the neighbors:stem cells and their niche.Cell 2004;116:769-778[PMID:15035980]
82 Li L,Neaves WB.Normal stem cells and cancer stem cells:the niche matters.Cancer Res 2006;66:4553-4557[PMID:16651403]
83 Kuhn NZ,Tuan RS.Regulation of stemness and stem cell niche of mesenchymal stem cells:implications in tumorigenesis and metastasis.J Cell Physiol 2010;222:268-277[PMID:19847802DOI:10.1002/jcp.21940]
84 Borovski T,De Sousa E Melo F,Vermeulen L,Medema JP.Cancer stem cell niche:the place to be.Cancer Res 2011;71:634-639[PMID:21266356 DOI:10.1158/0008-5472.CAN-10-3220]
85 Cabarcas SM,Mathews LA,Farrar WL.The cancer stem cell niche--there goes the neighborhood?Int J Cancer 2011;129:2315-2327[PMID:21792897 DOI:10.1002/ijc.26312]
86 Méndez-Ferrer S,Michurina TV,Ferraro F,Mazloom AR,Macarthur BD,Lira SA,Scadden DT,Ma’ayan A,Enikolopov GN,Frenette PS.Mesenchymal and haematopoietic stem cells form a unique bone marrow niche.Nature 2010;466:829-834[PMID:20703299 DOI:10.1038/nature09262]
87 Winkler IG,Sims NA,Pettit AR,Barbier V,Nowlan B,Helwani F,Poulton IJ,van Rooijen N,Alexander KA,Raggatt LJ,Lévesque JP.Bone marrow macrophages maintain hematopoietic stem cell(HSC)niches and their depletion mobilizes HSCs.Blood 2010;116:4815-4828[PMID:20713966 DOI:10.1182/blood-2009-11-253534]
88 Li HJ,Reinhardt F,Herschman HR,Weinberg RA.Cancerstimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling.Cancer Discov 2012;2:840-855[PMID:22763855 DOI:10.1158/2159-8290.CD-12-0101]
89 Wang R,Chadalavada K,Wilshire J,Kowalik U,Hovinga KE,Geber A,Fligelman B,Leversha M,Brennan C,Tabar V.Glioblastoma stem-like cells give rise to tumour endothelium.Nature 2010;468:829-833[PMID:21102433 DOI:10.1038/nature09624]
90 Domanska UM,Kruizinga RC,Nagengast WB,Timmer-Bosscha H,Huls G,de Vries EG,Walenkamp AM.A review on CXCR4/CXCL12 axis in oncology:no place to hide.Eur J Cancer 2013;49:219-230[PMID:22683307 DOI:10.1016/j.ejca.2012.05.005]
91 Gherardi E,Birchmeier W,Birchmeier C,Vande Woude G.Targeting MET in cancer:rationale and progress.Nat Rev Cancer2012;12:89-103[PMID:22270953 DOI:10.1038/nrc3205]
92 Jamieson C,Sharma M,Henderson BR.Wnt signaling from membrane to nucleus:β-catenin caught in a loop.Int J Biochem Cell Biol 2012;44:847-850[PMID:22433990 DOI:10.1016/j.biocel.2012.03.001]
93 Ono M,Kosaka N,Tominaga N,Yoshioka Y,Takeshita F,Takahashi RU,Yoshida M,Tsuda H,Tamura K,Ochiya T.Exosomes from bone marrow mesenchymal stem cells contain a micro RNA that promotes dormancy in metastatic breast cancer cells.Sci Signal 2014;7:ra63[PMID:24985346 DOI:10.1126/scisignal.2005231]
94 Nakano I,Garnier D,Minata M,Rak J.Extracellular vesicles in the biology of brain tumour stem cells--Implications for intercellular communication,therapy and biomarker development.Semin Cell Dev Biol 2015;40:17-26[PMID:25721810 DOI:10 .1016/j.semcdb.2015.02.011]
95 Grange C,Tapparo M,Collino F,Vitillo L,Damasco C,Deregibus MC,Tetta C,Bussolati B,Camussi G.Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche.Cancer Res 2011;71:5346-5356[PMID:21670082 DOI:10.1158/0008-5472.CAN-11-0241]
96 Kaplan RN,Riba RD,Zacharoulis S,Bramley AH,Vincent L,Costa C,Mac Donald DD,Jin DK,Shido K,Kerns SA,Zhu Z,Hicklin D,Wu Y,Port JL,Altorki N,Port ER,Ruggero D,Shmelkov SV,Jensen KK,Rafii S,Lyden D.VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche.Nature 2005;438:820-827[PMID:16341007]
97 Alderton GK.Metastasis.Exosomes drive premetastatic niche formation.Nat Rev Cancer 2012;12:447[PMID:22722393 DOI:10 .1038/nrc3304]
98 Thuma F,Z?ller M.Outsmart tumor exosomes to steal the cancer initiating cell its niche.Semin Cancer Biol 2014;28:39-50[PMID:24631836 DOI:10.1016/j.semcancer.2014.02.011]
99 Suchorska WM,Lach MS.The role of exosomes in tumor progression and metastasis(Review).Oncol Rep 2016;35:1237-1244[PMID:26707854 DOI:10.3892/or.2015.4507]
100 Jung T,Castellana D,Klingbeil P,Cuesta Hernández I,Vitacolonna M,Orlicky DJ,Roffler SR,Brodt P,Z?ller M.CD44v6 dependence of premetastatic niche preparation by exosomes.Neoplasia 2009;11:1093-1105[PMID:19794968]
101 Costa-Silva B,Aiello NM,Ocean AJ,Singh S,Zhang H,Thakur BK,Becker A,Hoshino A,Mark MT,Molina H,Xiang J,Zhang T,Theilen TM,García-Santos G,Williams C,Ararso Y,Huang Y,Rodrigues G,Shen TL,Labori KJ,Lothe IM,Kure EH,Hernandez J,Doussot A,Ebbesen SH,Grandgenett PM,Hollingsworth MA,Jain M,Mallya K,Batra SK,Jarnagin WR,Schwartz RE,Matei I,Peinado H,Stanger BZ,Bromberg J,Lyden D.Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver.Nat Cell Biol 2015;17:816-826[PMID:25985394 DOI:10.1038/ncb3169]
102 Vlassov AV,Magdaleno S,Setterquist R,Conrad R.Exosomes:current knowledge of their composition,biological functions,and diagnostic and therapeutic potentials.Biochim Biophys Acta 2012;1820:940-948[PMID:22503788 DOI:10.1016/j.bbagen.2012.03.017]
103 Lo Cicero A,Stahl PD,Raposo G.Extracellular vesicles shuffling intercellular messages:for good or for bad.Curr Opin Cell Biol2015;35:69-77[PMID:26001269 DOI:10.1016/j.ceb.2015.04.013]
104 Henne WM,Buchkovich NJ,Emr SD.The ESCRT pathway.Dev Cell 2011;21:77-91[PMID:21763610 DOI:10.1016/j.devcel.2011.05.015]
105 Colombo M,Moita C,van Niel G,Kowal J,Vigneron J,Benaroch P,Manel N,Moita LF,Théry C,Raposo G.Analysis of ESCRT functions in exosome biogenesis,composition and secretion highlights the heterogeneity of extracellular vesicles.J Cell Sci 2013;126:5553-5565[PMID:24105262 DOI:10.1242/jcs.128868]
106 Baietti MF,Zhang Z,Mortier E,Melchior A,Degeest G,Geeraerts A,Ivarsson Y,Depoortere F,Coomans C,Vermeiren E,Zimmermann P,David G.Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.Nat Cell Biol 2012;14:677-685[PMID:22660413 DOI:10.1038/ncb2502]
107 Z?ller M.Tetraspanins:push and pull in suppressing and promoting metastasis.Nat Rev Cancer 2009;9:40-55[PMID:19078974 DOI:10.1038/nrc2543]
108 van Niel G,Charrin S,Simoes S,Romao M,Rochin L,Saftig P,Marks MS,Rubinstein E,Raposo G.The tetraspanin CD63regulates ESCRT-independent and-dependent endosomal sorting during melanogenesis.Dev Cell 2011;21:708-721[PMID:21962903 DOI:10.1016/j.devcel.2011.08.019]
109 Chairoungdua A,Smith DL,Pochard P,Hull M,Caplan MJ.Exosome release ofβ-catenin:a novel mechanism that antagonizes Wnt signaling.J Cell Biol 2010;190:1079-1091[PMID:20837771 DOI:10.1083/jcb.201002049]
110 Kajimoto T,Okada T,Miya S,Zhang L,Nakamura S.Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes.Nat Commun2013;4:2712[PMID:24231649 DOI:10.1038/ncomms3712]
111 Kelly EE,Horgan CP,Goud B,Mc Caffrey MW.The Rab family of proteins:25 years on.Biochem Soc Trans 2012;40:1337-1347[PMID:23176478 DOI:10.1042/BST20120203]
112 Record M,Carayon K,Poirot M,Silvente-Poirot S.Exosomes a s n e w v e s i c u l a r l i p i d t r a n s p o r t e r s i n v o l v e d i n c e l l-c e l l communication and various pathophysiologies.Biochim Biophys Acta 2014;1841:108-120[PMID:24140720 DOI:10.1016/j.bbalip.2013.10.004]
113 Subra C,Grand D,Laulagnier K,Stella A,Lambeau G,Paillasse M,De Medina P,Monsarrat B,Perret B,Silvente-Poirot S,Poirot M,Record M.Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins.J Lipid Res 2010;51:2105-2120[PMID:20424270 DOI:10.1194/jlr.M003657]
114 Katzmann DJ,Odorizzi G,Emr SD.Receptor downregulation and multivesicular-body sorting.Nat Rev Mol Cell Biol 2002;3:893-905[PMID:12461556]
115 Costanzo M,Baryshnikova A,Bellay J,Kim Y,Spear ED,Sevier CS,Ding H,Koh JL,Toufighi K,Mostafavi S,Prinz J,St Onge RP,Vander Sluis B,Makhnevych T,Vizeacoumar FJ,Alizadeh S,Bahr S,Brost RL,Chen Y,Cokol M,Deshpande R,Li Z,Lin ZY,Liang W,Marback M,Paw J,San Luis BJ,Shuteriqi E,Tong AH,van Dyk N,Wallace IM,Whitney JA,Weirauch MT,Zhong G,Zhu H,Houry WA,Brudno M,Ragibizadeh S,Papp B,Pál C,Roth FP,Giaever G,Nislow C,Troyanskaya OG,Bussey H,Bader GD,Gingras AC,Morris QD,Kim PM,Kaiser CA,Myers CL,Andrews BJ,Boone C.The genetic landscape of a cell.Science 2010;327:425-431[PMID:20093466 DOI:10.1126/science.1180823]
116 Ramstedt B,Slotte JP.Membrane properties of sphingomyelins.FEBS Lett 2002;531:33-37[PMID:12401199]
117 Allen TM,Austin GA,Chonn A,Lin L,Lee KC.Uptake of liposomes by cultured mouse bone marrow macrophages:influence of liposome composition and size.Biochim Biophys Acta 1991;1061:56-64[PMID:1995057]
118 Chernomordik LV,Kozlov MM.Protein-lipid interplay in fusion and fission of biological membranes.Annu Rev Biochem 2003;72:175-207[PMID:14527322]
119 Subra C,Laulagnier K,Perret B,Record M.Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies.Biochimie 2007;89:205-212[PMID:17157973]
120 Trajkovic K,Hsu C,Chiantia S,Rajendran L,Wenzel D,Wieland F,Schwille P,Brügger B,Simons M.Ceramide triggers budding of exosome vesicles into multivesicular endosomes.Science 2008;319:1244-1247[PMID:18309083 DOI:10.1126/science.1153124]
121 Schey KL,Luther JM,Rose KL.Proteomics characterization of exosome cargo.Methods 2015;87:75-82[PMID:25837312 DOI:10 .1016/j.ymeth.2015.03.018]
122 Mathivanan S,Ji H,Simpson RJ.Exosomes:extracellular organelles important in intercellular communication.J Proteomics2 0 1 0;7 3:1907-1920[PMID:20601276 DOI:10.1016/j.jprot.2010.06.006]
123 Shen B,Fang Y,Wu N,Gould SJ.Biogenesis of the posterior pole is mediated by the exosome/microvesicle protein-sorting pathway.J Biol Chem 2011;286:44162-44176[PMID:21865156 DOI:10 .1074/jbc.M111.274803]
124 Rana S,Claas C,Kretz CC,Nazarenko I,Zoeller M.Activationinduced internalization differs for the tetraspanins CD9 and Tspan8:Impact on tumor cell motility.Int J Biochem Cell Biol 2011;43:106-119[PMID:20937409 DOI:10.1016/j.biocel.2010.10.002]
125 Guo BB,Bellingham SA,Hill AF.The neutral sphingomyelinase pathway regulates packaging of the prion protein into exosomes.J Biol Chem 2015;290:3455-3467[PMID:25505180 DOI:10 .1074/jbc.M114.605253]
126 Nabhan JF,Hu R,Oh RS,Cohen SN,Lu Q.Formation and release of arrestin domain-containing protein 1-mediated microvesicles(ARMMs)at plasma membrane by recruitment of TSG101 protein.Proc Natl Acad Sci USA 2012;109:4146-4151[PMID:22315426 DOI:10.1073/pnas.1200448109]
127 Shen B,Wu N,Yang JM,Gould SJ.Protein targeting to exosomes/microvesicles by plasma membrane anchors.J Biol Chem2011;286:14383-14395[PMID:21300796 DOI:10.1074/jbc.M110.208660]
128 Hoshino D,Kirkbride KC,Costello K,Clark ES,Sinha S,GregaLarson N,Tyska MJ,Weaver AM.Exosome secretion is enhanced by invadopodia and drives invasive behavior.Cell Rep 2013;5:1159-1168[PMID:24290760 DOI:10.1016/j.celrep.2013.10.050]
129 Rana S,Yue S,Stadel D,Z?ller M.Toward tailored exosomes:the exosomal tetraspanin web contributes to target cell selection.Int J Biochem Cell Biol 2012;44:1574-1584[PMID:22728313 DOI:10 .1016/j.biocel.2012.06.018]
130 Yue S,Mu W,Erb U,Z?ller M.The tetraspanins CD151 and Tspan8 are essential exosome components for the crosstalk between cancer initiating cells and their surrounding.Oncotarget2015;6:2366-2384[PMID:25544774]
131 Choi DS,Yang JS,Choi EJ,Jang SC,Park S,Kim OY,Hwang D,Kim KP,Kim YK,Kim S,Gho YS.The protein interaction network of extracellular vesicles derived from human colorectal cancer cells.J Proteome Res 2012;11:1144-1151[PMID:22149170 DOI:10 .1021/pr200842h]
132 Ji H,Greening DW,Barnes TW,Lim JW,Tauro BJ,Rai A,Xu R,Adda C,Mathivanan S,Zhao W,Xue Y,Xu T,Zhu HJ,Simpson RJ.Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components.Proteomics 2013;13:1672-1686[PMID:23585443 DOI:10.1002/pmic.201200562]
133 Al-Nedawi K,Meehan B,Micallef J,Lhotak V,May L,Guha A,Rak J.Intercellular transfer of the oncogenic receptor EGFRv III by microvesicles derived from tumour cells.Nat Cell Biol 2008;10:619-624[PMID:18425114 DOI:10.1038/ncb1725]
134 Corcoran C,Rani S,O’Brien K,O’Neill A,Prencipe M,Sheikh R,Webb G,Mc Dermott R,Watson W,Crown J,O’Driscoll L.Docetaxel-resistance in prostate cancer:evaluating associated phenotypic changes and potential for resistance transfer via exosomes.PLo S One 2012;7:e50999[PMID:23251413 DOI:10 .1371/journal.pone.0050999]
135 Park JA,Sharif AS,Tschumperlin DJ,Lau L,Limbrey R,Howarth P,Drazen JM.Tissue factor-bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo.J Allergy Clin Immunol 2012;130:1375-1383[PMID:22828416 DOI:10.1016/j.jaci.2012.05.031]
136 Demory Beckler M,Higginbotham JN,Franklin JL,Ham AJ,Halvey PJ,Imasuen IE,Whitwell C,Li M,Liebler DC,Coffey RJ.Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.Mol Cell Proteomics 2013;12:343-355[PMID:23161513 DOI:10.1074/mcp.M112.022806]
137 Kumar D,Gupta D,Shankar S,Srivastava RK.Biomolecular characterization of exosomes released from cancer stem cells:Possible implications for biomarker and treatment of cancer.Oncotarget 2015;6:3280-3291[PMID:25682864]
138 Z?ller M.Exosomes in Cancer Disease.Methods Mol Biol 2016;1381:111-149[PMID:26667458 DOI:10.1007/978-1-4939-3204-7 _7]
139 Gibbings DJ,Ciaudo C,Erhardt M,Voinnet O.Multivesicular bodies associate with components of mi RNA effector complexes and modulate mi RNA activity.Nat Cell Biol 2009;11:1143-1149[PMID:19684575 DOI:10.1038/ncb1929]
140 Balaj L,Lessard R,Dai L,Cho YJ,Pomeroy SL,Breakefield XO,Skog J.Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences.Nat Commun 2011;2:180[PMID:21285958 DOI:10.1038/ncomms1180]
141 Salido-Guadarrama I,Romero-Cordoba S,Peralta-Zaragoza O,Hidalgo-Miranda A,Rodríguez-Dorantes M.Micro RNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer.Onco Targets Ther 2014;7:1327-1338[PMID:25092989 DOI:10.2147/OTT.S61562]
142 Valadi H,Ekstr?m K,Bossios A,Sj?strand M,Lee JJ,L?tvall JO.Exosome-mediated transfer of m RNAs and micro RNAs is a novel mechanism of genetic exchange between cells.Nat Cell Biol 2007;9:654-659[PMID:17486113]
143 Turchinovich A,Weiz L,Langheinz A,Burwinkel B.Characterization of extracellular circulating micro RNA.Nucleic Acids Res 2011;39:7223-7233[PMID:21609964 DOI:10.1093/nar/gkr254]
144 Vedeler A,Holl?s H,Grindheim AK,Raddum AM.Multiple roles of annexin A2 in post-transcriptional regulation of gene expression.Curr Protein Pept Sci 2012;13:401-412[PMID:22708494]
145 Villarroya-Beltri C,Gutiérrez-Vázquez C,Sánchez-Cabo F,Pérez-Hernández D,Vázquez J,Martin-Cofreces N,MartinezHerrera DJ,Pascual-Montano A,Mittelbrunn M,Sánchez-Madrid F.Sumoylated hn RNPA2B1 controls the sorting of mi RNAs into exosomes through binding to specific motifs.Nat Commun 2013;4:2980[PMID:24356509 DOI:10.1038/ncomms3980]
146 Kogure T,Yan IK,Lin WL,Patel T.Extracellular VesicleMediated Transfer of a Novel Long Noncoding RNA TUC339:A Mechanism of Intercellular Signaling in Human Hepatocellular Cancer.Genes Cancer 2013;4:261-272[PMID:24167654 DOI:10 .1177/1947601913499020]
147 Pinto R,De Summa S,Petriella D,Tudoran O,Danza K,Tommasi S.The value of new high-throughput technologies for diagnosis and prognosis in solid tumors.Cancer Biomark 2014;14:103-117[PMID:24878811 DOI:10.3233/CBM-130328]
148 Iwakawa HO,Tomari Y.The Functions of Micro RNAs:m RNA Decay and Translational Repression.Trends Cell Biol 2015;25:651-665[PMID:26437588 DOI:10.1016/j.tcb.2015.07.011]
149 Sato-Kuwabara Y,Melo SA,Soares FA,Calin GA.The fusion of two worlds:non-coding RNAs and extracellular vesicles--diagnostic and therapeutic implications(Review).Int J Oncol2015;46:17-27[PMID:25338714 DOI:10.3892/ijo.2014.2712]
150 Garg M.Targeting micro RNAs in epithelial-to-mesenchymal transition-induced cancer stem cells:therapeutic approaches in cancer.Expert Opin Ther Targets 2015;19:285-297[PMID:25563894 DOI:10.1517/14728222.2014.975794]
151 Garofalo M,Croce CM.Role of micro RNAs in maintaining cancer stem cells.Adv Drug Deliv Rev 2015;81:53-61[PMID:25446141 DOI:10.1016/j.addr.2014.11.014]
152 Katoh M.Therapeutics targeting angiogenesis:genetics and epigenetics,extracellular mi RNAs and signaling networks(Review).Int J Mol Med 2013;32:763-767[PMID:23863927DOI:10.3892/ijmm.2013.1444]
153 Palma J,Yaddanapudi SC,Pigati L,Havens MA,Jeong S,Weiner GA,Weimer KM,Stern B,Hastings ML,Duelli DM.Micro RNAs are exported from malignant cells in customized particles.Nucleic Acids Res 2012;40:9125-9138[PMID:22772984 DOI:10.1093/nar/gks656]
154 Rappa G,Mercapide J,Anzanello F,Pope RM,Lorico A.Biochemical and biological characterization of exosomes containing prominin-1/CD133.Mol Cancer 2013;12:62[PMID:23767874 DOI:10.1186/1476-4598-12-62]
155 Silva A,Bullock M,Calin G.The Clinical Relevance of Long Non-Coding RNAs in Cancer.Cancers(Basel)2015;7:2169-2182[PMID:26516918 DOI:10.3390/cancers7040884]
156 Fitzgerald TL,Mc Cubrey JA.Pancreatic cancer stem cells:association with cell surface markers,prognosis,resistance,metastasis and treatment.Adv Biol Regul 2014;56:45-50[PMID:24925031 DOI:10.1016/j.jbior.2014.05.001]
157 Abel EV,Simeone DM.Biology and clinical applications of pancreatic cancer stem cells.Gastroenterology 2013;144:1241-1248[PMID:23622133 DOI:10.1053/j.gastro.2013.01.072]
158 Ohara Y,Oda T,Sugano M,Hashimoto S,Enomoto T,Yamada K,Akashi Y,Miyamoto R,Kobayashi A,Fukunaga K,Morishita Y,Ohkohchi N.Histological and prognostic importance of CD44(+)/CD24(+)/Ep CAM(+)expression in clinical pancreatic cancer.Cancer Sci 2013;104:1127-1134[PMID:23679813 DOI:10.1111/cas.12198]
159 Hori Y.Prominin-1(CD133)Reveals New Faces of Pancreatic Progenitor Cells and Cancer Stem Cells:Current Knowledge and Therapeutic Perspectives.Adv Exp Med Biol 2013;777:185-196[PMID:23161083 DOI:10.1007/978-1-4614-5894-4_12]
160 Balic A,Dorado J,Alonso-Gómez M,Heeschen C.Stem cells as the root of pancreatic ductal adenocarcinoma.Exp Cell Res 2012;318:691-704[PMID:22119145 DOI:10.1016/j.yexcr.2011.11.007]
161 Vaz AP,Ponnusamy MP,Seshacharyulu P,Batra SK.A concise review on the current understanding of pancreatic cancer stem cells.J Cancer Stem Cell Res 2014;2:e1004[PMID:26451384]
162 Wang H,Rana S,Giese N,Büchler MW,Z?ller M.Tspan8,CD44v6 and alpha6beta4 are biomarkers of migrating pancreatic cancer-initiating cells.Int J Cancer 2013;133:416-426[PMID:23338841 DOI:10.1002/ijc.28044]
163 Li C,Wu JJ,Hynes M,Dosch J,Sarkar B,Welling TH,Pasca di Magliano M,Simeone DM.c-Met is a marker of pancreatic cancer stem cells and therapeutic target.Gastroenterology2011;141:2218-2227.e5[PMID:21864475 DOI:10.1053/j.gastro.2011.08.009]
164 Saito S,Okabe H,Watanabe M,Ishimoto T,Iwatsuki M,Baba Y,Tanaka Y,Kurashige J,Miyamoto Y,Baba H.CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer.Oncol Rep 2013;29:1570-1578[PMID:23404221 DOI:10.3892/or.2013.2273]
165 Todaro M,Gaggianesi M,Catalano V,Benfante A,Iovino F,Biffoni M,Apuzzo T,Sperduti I,Volpe S,Cocorullo G,Gulotta G,Dieli F,De Maria R,Stassi G.CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis.Cell Stem Cell 2014;14:342-356[PMID:24607406DOI:10.1016/j.stem.2014.01.009]
166 Dalla Pozza E,Dando I,Biondani G,Brandi J,Costanzo C,Zoratti E,Fassan M,Boschi F,Melisi D,Cecconi D,Scupoli MT,Scarpa A,Palmieri M.Pancreatic ductal adenocarcinoma cell lines display a plastic ability to bi-directionally convert into cancer stem cells.Int J Oncol 2015;46:1099-1108[PMID:25502497 DOI:10.3892/ijo.2014.2796]
167 Klingbeil P,Marhaba R,Jung T,Kirmse R,Ludwig T,Z?ller M.CD44 variant isoforms promote metastasis formation by a tumor cell-matrix cross-talk that supports adhesion and apoptosis resistance.Mol Cancer Res 2009;7:168-179[PMID:19208744DOI:10.1158/1541-7786.MCR-08-0207]
168 Matzke-Ogi A,Jannasch K,Shatirishvili M,Fuchs B,Chiblak S,Morton J,Tawk B,Lindner T,Sansom O,Alves F,Warth A,Schwager C,Mier W,Kleeff J,Ponta H,Abdollahi A,OrianRousseau V.Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling.Gastroenterology 2016;150:513-25.e10[PMID:26597578 DOI:10 .1053/j.gastro.2015.10.020]
169 Chen K,Li Z,Jiang P,Zhang X,Zhang Y,Jiang Y,He Y,Li X.Co-expression of CD133,CD44v6 and human tissue factor is associated with metastasis and poor prognosis in pancreatic carcinoma.Oncol Rep 2014;32:755-763[PMID:24920554 DOI:10 .3892/or.2014.3245]
170 Aruffo A,Stamenkovic I,Melnick M,Underhill CB,Seed B.CD44 is the principal cell surface receptor for hyaluronate.Cell1990;61:1303-1313[PMID:1694723]
171 Ishii S,Ford R,Thomas P,Nachman A,Steele G,Jessup JM.CD44 participates in the adhesion of human colorectal carcinoma cells to laminin and type IV collagen.Surg Oncol 1993;2:255-264[PMID:7504563]
172 Jalkanen S,Jalkanen M.Lymphocyte CD44 binds the COOHterminal heparin-binding domain of fibronectin.J Cell Biol 1992;116:817-825[PMID:1730778]
173 Konstantopoulos K,Thomas SN.Cancer cells in transit:the vascular interactions of tumor cells.Annu Rev Biomed Eng2009;11:177-202[PMID:19413512 DOI:10.1146/annurevbioeng-061008-124949]
174 Kim MS,Park MJ,Moon EJ,Kim SJ,Lee CH,Yoo H,Shin SH,Song ES,Lee SH.Hyaluronic acid induces osteopontin via the phosphatidylinositol 3-kinase/Akt pathway to enhance the motility of human glioma cells.Cancer Res 2005;65:686-691[PMID:15705860]
175 Khan SA,Cook AC,Kappil M,Günthert U,Chambers AF,Tuck AB,Denhardt DT.Enhanced cell surface CD44 variant(v6,v9)expression by osteopontin in breast cancer epithelial cells facilitates tumor cell migration:novel post-transcriptional,posttranslational regulation.Clin Exp Metastasis 2005;22:663-673[PMID:16691370]
176 Tremmel M,Matzke A,Albrecht I,Laib AM,Olaku V,BallmerHofer K,Christofori G,Héroult M,Augustin HG,Ponta H,Orian-Rousseau V.A CD44v6 peptide reveals a role of CD44 in VEGFR-2 signaling and angiogenesis.Blood 2009;114:5236-5244[PMID:19773544 DOI:10.1182/blood-2009-04-219204]
177 Z?ller M.CD44:can a cancer-initiating cell profit from an abundantly expressed molecule?Nat Rev Cancer 2011;11:254-267[PMID:21390059 DOI:10.1038/nrc3023]
178 Kollet O,Dar A,Shivtiel S,Kalinkovich A,Lapid K,Sztainberg Y,Tesio M,Samstein RM,Goichberg P,Spiegel A,Elson A,Lapidot T.Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells.Nat Med 2006;12:657-664[PMID:16715089]
179 Weber GF,Bronson RT,Ilagan J,Cantor H,Schmits R,Mak TW.Absence of the CD44 gene prevents sarcoma metastasis.Cancer Res 2002;62:2281-2286[PMID:11956084]
180 Williams K,Motiani K,Giridhar PV,Kasper S.CD44 integrates signaling in normal stem cell,cancer stem cell and(pre)metastatic niches.Exp Biol Med(Maywood)2013;238:324-338[PMID:23598979 DOI:10.1177/1535370213480714]
181 Trusolino L,Bertotti A,Comoglio PM.MET signalling:principles and functions in development,organ regeneration and cancer.Nat Rev Mol Cell Biol 2010;11:834-848[PMID:21102609 DOI:10 .1038/nrm3012]
182 Lokeshwar VB,Fregien N,Bourguignon LY.Ankyrin-binding domain of CD44(GP85)is required for the expression of hyaluronic acid-mediated adhesion function.J Cell Biol 1994;126:1099-1109[PMID:7519619]
183 Fehon RG,Mc Clatchey AI,Bretscher A.Organizing the cell cortex:the role of ERM proteins.Nat Rev Mol Cell Biol 2010;11:276-287[PMID:20308985 DOI:10.1038/nrm2866]
184 Mori T,Kitano K,Terawaki S,Maesaki R,Fukami Y,Hakoshima T.Structural basis for CD44 recognition by ERM proteins.J Biol Chem 2008;283:29602-29612[PMID:18753140 DOI:10.1074/jbc.M803606200]
185 Nagano O,Saya H.Mechanism and biological significance of CD44 cleavage.Cancer Sci 2004;95:930-935[PMID:15596040]
186 Okamoto I,Kawano Y,Murakami D,Sasayama T,Araki N,Miki T,Wong AJ,Saya H.Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway.J Cell Biol 2001;155:755-762[PMID:11714729]
187 Miletti-González KE,Murphy K,Kumaran MN,Ravindranath AK,Wernyj RP,Kaur S,Miles GD,Lim E,Chan R,Chekmareva M,Heller DS,Foran D,Chen W,Reiss M,Bandera EV,Scotto K,Rodríguez-Rodríguez L.Identification of function for CD44intracytoplasmic domain(CD44-ICD):modulation of matrix metalloproteinase 9(MMP-9)transcription via novel promoter response element.J Biol Chem 2012;287:18995-19007[PMID:22433859 DOI:10.1074/jbc.M111.318774]
188 Pietras A,Katz AM,Ekstr?m EJ,Wee B,Halliday JJ,Pitter KL,Werbeck JL,Amankulor NM,Huse JT,Holland EC.OsteopontinCD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth.Cell Stem Cell 2014;14:357-369[PMID:24607407 DOI:10.1016/j.stem.2014.01.005]
189 Oliferenko S,Paiha K,Harder T,Gerke V,Schw?rzler C,Schwarz H,Beug H,Günthert U,Huber LA.Analysis of CD44-containing lipid rafts:Recruitment of annexin II and stabilization by the actin cytoskeleton.J Cell Biol 1999;146:843-854[PMID:10459018]
190 Zarbock A,Ley K,Mc Ever RP,Hidalgo A.Leukocyte ligands for endothelial selectins:specialized glycoconjugates that mediate rolling and signaling under flow.Blood 2011;118:6743-6751[PMID:22021370 DOI:10.1182/blood-2011-07-343566]
191 F?ger N,Marhaba R,Z?ller M.Involvement of CD44 in cytoskeleton rearrangement and raft reorganization in T cells.J Cell Sci 2001;114:1169-1178[PMID:11228160]
192 Róg T,Vattulainen I.Cholesterol,sphingolipids,and glycolipids:what do we know about their role in raft-like membranes?Chem Phys Lipids 2014;184:82-104[PMID:25444976 DOI:10.1016/j.chemphyslip.2014.10.004]
193 Lin ML,Lu YC,Chen HY,Lee CC,Chung JG,Chen SS.Suppressing the formation of lipid raft-associated Rac1/PI3K/Akt signaling complexes by curcumin inhibits SDF-1α-induced invasion of human esophageal carcinoma cells.Mol Carcinog2014;53:360-379[PMID:23192861 DOI:10.1002/mc.21984]
194 Ratajczak MZ,Lee H,Wysoczynski M,Wan W,Marlicz W,Laughlin MJ,Kucia M,Janowska-Wieczorek A,Ratajczak J.Novel insight into stem cell mobilization-plasma sphingosine-1 -phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex.Leukemia 2010;24:976-985[PMID:20357827 DOI:10.1038/leu.2010.53]
195 Desai B,Ma T,Zhu J,Chellaiah MA.Characterization of the expression of variant and standard CD44 in prostate cancer cells:identification of the possible molecular mechanism of CD44/MMP9 complex formation on the cell surface.J Cell Biochem2009;108:272-284[PMID:19582779 DOI:10.1002/jcb.22248]
196 Bourguignon LY,Gunja-Smith Z,Iida N,Zhu HB,Young LJ,Muller WJ,Cardiff RD.CD44v(3,8-10)is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase(MMP-9)association in metastatic breast cancer cells.J Cell Physiol 1998;176:206-215[PMID:9618160]
197 Zarzynska JM.Two faces of TGF-beta1 in breast cancer.Mediators Inflamm 2014;2014:141747[PMID:24891760 DOI:10 .1155/2014/141747]
198 Takahashi E,Nagano O,Ishimoto T,Yae T,Suzuki Y,Shinoda T,Nakamura S,Niwa S,Ikeda S,Koga H,Tanihara H,Saya H.Tumor necrosis factor-alpha regulates transforming growth factorbeta-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-moesin interaction.J Biol Chem 2010;285:4060-4073[PMID:19965872 DOI:10.1074/jbc.M109.056523]
199 Z?ller M.CD44,Hyaluronan,the Hematopoietic Stem Cell,and Leukemia-Initiating Cells.Front Immunol 2015;6:235[PMID:26074915 DOI:10.3389/fimmu.2015.00235]
200 Rutnam ZJ,Yang BB.The non-coding 3’UTR of CD44 induces metastasis by regulating extracellular matrix functions.J Cell Sci2012;125:2075-2085[PMID:22637644 DOI:10.1242/jcs100818]
201 Bourguignon LY,Earle C,Wong G,Spevak CC,Krueger K.Stem cell marker(Nanog)and Stat-3 signaling promote Micro RNA-21expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells.Oncogene 2012;31:149-160[PMID:21685938 DOI:10.1038/onc.2011.222]
202 Rana S,Malinowska K,Z?ller M.Exosomal tumor micro RNA modulates premetastatic organ cells.Neoplasia 2013;15:281-295[PMID:23479506 DOI:10.1593/neo.122010]
203 Delitto D,Vertes-George E,Hughes SJ,Behrns KE,Trevino JG.c-Met signaling in the development of tumorigenesis and chemoresistance:potential applications in pancreatic cancer.World J Gastroenterol 2014;20:8458-8470[PMID:25024602 DOI:10 .3748/wjg.v20.i26.8458]
204 Orian-Rousseau V,Morrison H,Matzke A,Kastilan T,Pace G,Herrlich P,Ponta H.Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin.Mol Biol Cell 2007;18:76-83[PMID:17065554 DOI:10 .1091/mbc.E06-08-0674]
205 Maroun CR,Rowlands T.The Met receptor tyrosine kinase:a key player in oncogenesis and drug resistance.Pharmacol Ther 2014;142:316-338[PMID:24384534 DOI:10.1016/j.pharmthera.2013.12.014]
206 Marano L,Chiari R,Fabozzi A,De Vita F,Boccardi V,Roviello G,Petrioli R,Marrelli D,Roviello F,Patriti A.c-Met targeting in advanced gastric cancer:An open challenge.Cancer Lett 2015;365:30-36[PMID:26049023 DOI:10.1016/j.canlet.2015.05.028]
207 Jung T,Gross W,Z?ller M.CD44v6 coordinates tumor matrixtriggered motility and apoptosis resistance.J Biol Chem 2011;286:15862-15874[PMID:21372142 DOI:10.1074/jbc.M110.208421]
208 Ni J,Cozzi PJ,Hao JL,Beretov J,Chang L,Duan W,Shigdar S,Delprado WJ,Graham PH,Bucci J,Kearsley JH,Li Y.CD44variant 6 is associated with prostate cancer metastasis and chemo-/radioresistance.Prostate 2014;74:602-617[PMID:24615685DOI:10.1002/pros.22775]
209 Hasenauer S,Malinger D,Koschut D,Pace G,Matzke A,von Au A,Orian-Rousseau V.Internalization of Met requires the co-receptor CD44v6 and its link to ERM proteins.PLo S One 2013;8:e62357[PMID:23626807 DOI:10.1371/journal.pone.0062357]
210 Dallas NA,Xia L,Fan F,Gray MJ,Gaur P,van Buren G,Samuel S,Kim MP,Lim SJ,Ellis LM.Chemoresistant colorectal cancer cells,the cancer stem cell phenotype,and increased sensitivity to insulin-like growth factor-I receptor inhibition.Cancer Res2009;69:1951-1957[PMID:19244128 DOI:10.1158/0008-5472.CAN-08-2023]
211 Porsch H,Mehi?M,Olofsson B,Heldin P,Heldin CH.Plateletderived growth factorβ-receptor,transforming growth factorβtype I receptor,and CD44 protein modulate each other’s signaling and stability.J Biol Chem 2014;289:19747-19757[PMID:24860093 DOI:10.1074/jbc.M114.547273]
212 Sakai K,Aoki S,Matsumoto K.Hepatocyte growth factor and Met in drug discovery.J Biochem 2015;157:271-284[PMID:25770121 DOI:10.1093/jb/mvv027]
213 Maecker HT,Todd SC,Levy S.The tetraspanin superfamily:molecular facilitators.FASEB J 1997;11:428-442[PMID:9194523]
214 Hemler ME.Tetraspanin proteins promote multiple cancer stages.Nat Rev Cancer 2014;14:49-60[PMID:24505619]
215 Wang HX,Li Q,Sharma C,Knoblich K,Hemler ME.Tetraspanin protein contributions to cancer.Biochem Soc Trans 2011;39:547-552[PMID:21428937 DOI:10.1042/BST0390547]
216 Guo Q,Xia B,Zhang F,Richardson MM,Li M,Zhang JS,Chen F,Zhang XA.Tetraspanin CO-029 inhibits colorectal cancer cell movement by deregulating cell-matrix and cell-cell adhesions.PLo S One 2012;7:e38464[PMID:22679508 DOI:10.1371/journal.pone.0038464]
217 Berthier-Vergnes O,Kharbili ME,de la Fouchardière A,Pointecouteau T,Verrando P,Wierinckx A,Lachuer J,Le Naour F,Lamartine J.Gene expression profiles of human melanoma cells with different invasive potential reveal TSPAN8 as a novel mediator of invasion.Br J Cancer 2011;104:155-165[PMID:21081927 DOI:10.1038/sj.bjc.6605994]
218 Sterk LM,Geuijen CA,van den Berg JG,Claessen N,Weening JJ,Sonnenberg A.Association of the tetraspanin CD151 with the laminin-binding integrins alpha3beta1,alpha6beta1,alpha6beta4and alpha7beta1 in cells in culture and in vivo.J Cell Sci 2002;115:1161-1173[PMID:11884516]
219 Liu L,He B,Liu WM,Zhou D,Cox JV,Zhang XA.Tetraspanin CD151 promotes cell migration by regulating integrin trafficking.J Biol Chem 2007;282:31631-31642[PMID:17716972 DOI:10 .1074/jbc.M701165200]
220 Zijlstra A,Lewis J,Degryse B,Stuhlmann H,Quigley JP.The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151.Cancer Cell 2008;13:221-234[PMID:18328426 DOI:10.1016/j.ccr.2008.01.031]
221 Hong IK,Jeoung DI,Ha KS,Kim YM,Lee H.Tetraspanin CD151stimulates adhesion-dependent activation of Ras,Rac,and Cdc42by facilitating molecular association betweenβ1 integrins and small GTPases.J Biol Chem 2012;287:32027-32039[PMID:22843693 DOI:10.1074/jbc.M111.314443]
222 Yang XH,Mirchev R,Deng X,Yacono P,Yang HL,Golan DE,Hemler ME.CD151 restricts theα6 integrin diffusion mode.J Cell Sci 2012;125:1478-1487[PMID:22328509 DOI:10.1242/jcs.093963]
223 Wei L,Li Y,Suo Z.TSPAN8 promotes gastric cancer growth and metastasis via ERK MAPK pathway.Int J Clin Exp Med 2015;8:8599-8607[PMID:26309511]
224 Kim TK,Park CS,Jeoung MH,Lee WR,Go NK,Choi JR,Lee TS,Shim H,Lee S.Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells.Biochem Biophys Res Commun 2015;468:774-780[PMID:26562525 DOI:10.1016/j.bbrc.2015.11.031]
225 Zhu H,Wu Y,Zheng W,Lu S.CO-029 is overexpressed in gastric cancer and mediates the effects of EGF on gastric cancer cell proliferation and invasion.Int J Mol Med 2015;35:798-802[PMID:25592989 DOI:10.3892/ijmm.2015.2069]
226 Zhou Z,Ran YL,Hu H,Pan J,Li ZF,Chen LZ,Sun LC,Peng L,Zhao XL,Yu L,Sun LX,Yang ZH.TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression.Clin Exp Metastasis 2008;25:537-548[PMID:18365756 DOI:10 .1007/s10585-008-9168-0]
227 Hemler ME.Tetraspanin functions and associated microdomains.Nat Rev Mol Cell Biol 2005;6:801-811[PMID:16314869 DOI:10 .1038/nrm1736]
228 Levy S,Shoham T.Protein-protein interactions in the tetraspanin web.Physiology(Bethesda)2005;20:218-224[PMID:16024509DOI:10.1152/physiol.00015.2005]
229 Stipp CS,Kolesnikova TV,Hemler ME.Functional domains in tetraspanin proteins.Trends Biochem Sci 2003;28:106-112[PMID:12575999 DOI:10.1016/S0968-0004(02)00014-2]
230 Seigneuret M.Complete predicted three-dimensional structure of the facilitator transmembrane protein and hepatitis C virus receptor CD81:conserved and variable structural domains in the tetraspanin superfamily.Biophys J 2006;90:212-227[PMID:16352525 DOI:10 .1529/biophysj.105.069666]
231 Berditchevski F,Odintsova E,Sawada S,Gilbert E.Expression of the palmitoylation-deficient CD151 weakens the association of alpha 3 beta 1 integrin with the tetraspanin-enriched microdomains and affects integrin-dependent signaling.J Biol Chem 2002;277:36991-37000[PMID:12110679 DOI:10.1074/jbc.M205265200]
232 Delandre C,Penabaz TR,Passarelli AL,Chapes SK,Clem RJ.Mutation of juxtamembrane cysteines in the tetraspanin CD81affects palmitoylation and alters interaction with other proteins at the cell surface.Exp Cell Res 2009;315:1953-1963[PMID:19328198 DOI:10.1016/j.yexcr.2009.03.013]
233 Sharma C,Yang XH,Hemler ME.DHHC2 affects palmitoylation,stability,and functions of tetraspanins CD9 and CD151.Mol Biol Cell 2008;19:3415-3425[PMID:18508921 DOI:10.1091/mbc.E07-11-1164]
234 Todeschini AR,Dos Santos JN,Handa K,Hakomori SI.Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/c Met-mediated pathway.Proc Natl Acad Sci USA 2008;105:1925-1930[PMID:18272501 DOI:10.1073/pnas.0709619104]
235 Wang XQ,Yan Q,Sun P,Liu JW,Go L,Mc Daniel SM,Paller AS.Suppression of epidermal growth factor receptor signaling by protein kinase C-alpha activation requires CD82,caveolin-1,and ganglioside.Cancer Res 2007;67:9986-9995[PMID:17942932DOI:10.1158/0008-5472.CAN-07-1300]
236 Delaguillaumie A,Harriague J,Kohanna S,Bismuth G,Rubinstein E,Seigneuret M,Conjeaud H.Tetraspanin CD82 controls the association of cholesterol-dependent microdomains with the actin cytoskeleton in T lymphocytes:relevance to co-stimulation.J Cell Sci 2004;117:5269-5282[PMID:15454569 DOI:10.1242/jcs.01380]
237 Escola JM,Kleijmeer MJ,Stoorvogel W,Griffith JM,Yoshie O,Geuze HJ.Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.J Biol Chem 1998;273:20121-20127[PMID:9685355 DOI:10.1074/jbc.273.32.20121]
238 Berditchevski F,Odintsova E.Tetraspanins as regulators of protein trafficking.Traffic 2007;8:89-96[PMID:17181773 DOI:10 .1111/j.1600-0854.2006.00515.x]
239 Marks MS,Ohno H,Kirchnausen T,Bonracino JS.Protein sorting by tyrosine-based signals:adapting to the Ys and wherefores.Trends Cell Biol 1997;7:124-128[PMID:17708922 DOI:10 .1016/S0962-8924(96)10057-X]
240 Charrin S,le Naour F,Silvie O,Milhiet PE,Boucheix C,Rubinstein E.Lateral organization of membrane proteins:tetraspanins spin their web.Biochem J 2009;420:133-154[PMID:19426143 DOI:10.1042/BJ20082422]
241 Berditchevski F.Complexes of tetraspanins with integrins:more than meets the eye.J Cell Sci 2001;114:4143-4151[PMID:11739647]
242 Bassani S,Cingolani LA.Tetraspanins:Interactions and interplay with integrins.Int J Biochem Cell Biol 2012;44:703-708[PMID:22326999 DOI:10.1016/j.biocel.2012.01.020]
243 Herlevsen M,Schmidt DS,Miyazaki K,Z?ller M.The association of the tetraspanin D6.1A with the alpha6beta4 integrin supports cell motility and liver metastasis formation.J Cell Sci 2003;116:4373-4390[PMID:13130099 DOI:10.1242/jcs.00760]
244 Gesierich S,Paret C,Hildebrand D,Weitz J,Zgraggen K,SchmitzWinnenthal FH,Horejsi V,Yoshie O,Herlyn D,Ashman LK,Z?ller M.Colocalization of the tetraspanins,CO-029 and CD151,with integrins in human pancreatic adenocarcinoma:impact on cell motility.Clin Cancer Res 2005;11:2840-2852[PMID:15837731DOI:10.1158/1078-0432.CCR-04-1935]
245 Yue S,Mu W,Z?ller M.Tspan8 and CD151 promote metastasis by distinct mechanisms.Eur J Cancer 2013;49:2934-2948[PMID:23683890 DOI:10.1016/j.ejca.2013.03.032]
246 Gesierich S,Berezovskiy I,Ryschich E,Z?ller M.Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029.Cancer Res 2006;66:7083-7094[PMID:16849554 DOI:10 .1158/0008-5472.CAN-06-0391]
247 Nazarenko I,Rana S,Baumann A,Mc Alear J,Hellwig A,Trendelenburg M,Lochnit G,Preissner KT,Z?ller M.Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation.Cancer Res 2010;70:1668-1678[PMID:20124479 DOI:10.1158/0008-5472.CAN-09-2470]
248 Yá?ez-MóM,Gutiérrez-López MD,Caba?as C.Functional interplay between tetraspanins and proteases.Cell Mol Life Sci2011;68:3323-3335[PMID:21687991 DOI:10.1007/s00018-011 -0746-y]
249 Le Naour F,AndréM,Greco C,Billard M,Sordat B,Emile JF,Lanza F,Boucheix C,Rubinstein E.Profiling of the tetraspanin web of human colon cancer cells.Mol Cell Proteomics 2006;5:845-857[PMID:16467180 DOI:10.1074/mcp.M500330-MCP200]
250 Wang GP,Han XF.CD9 modulates proliferation of human glioblastoma cells via epidermal growth factor receptor signaling.Mol Med Rep 2015;12:1381-1386[PMID:25760022 DOI:10 .3892/mmr.2015.3466]
251 Sridhar SC,Miranti CK.Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases.Oncogene 2006;25:2367-2378[PMID:16331263 DOI:10.1038/sj.onc.1209269]
252 Little KD,Hemler ME,Stipp CS.Dynamic regulation of a GPCRtetraspanin-G protein complex on intact cells:central role of CD81 in facilitating GPR56-Galpha q/11 association.Mol Biol Cell 2004;15:2375-2387[PMID:15004227 DOI:10.1091/mbc.E03-12-0886]
253 Feng S,Agoulnik IU,Truong A,Li Z,Creighton CJ,Kaftanovskaya EM,Pereira R,Han HD,Lopez-Berestein G,Klonisch T,Ittmann MM,Sood AK,Agoulnik AI.Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis.Endocr Relat Cancer 2010;17:1021-1033[PMID:20861284 DOI:10.1677/ERC-10-0073]
254 AndréM,Le Caer JP,Greco C,Planchon S,El Nemer W,Boucheix C,Rubinstein E,Chamot-Rooke J,Le Naour F.Proteomic analysis of the tetraspanin web using LC-ESI-MS/MS and MALDI-FTICR-MS.Proteomics 2006;6:1437-1449[PMID:16404722 DOI:10.1002/pmic.200500180]
255 Zhang XA,Bontrager AL,Hemler ME.Transmembrane-4superfamily proteins associate with activated protein kinase C(PKC)and link PKC to specific beta(1)integrins.J Biol Chem2001;276:25005-25013[PMID:11325968 DOI:10.1074/jbc.M102156200]
256 Claas C,Stipp CS,Hemler ME.Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts.J Biol Chem 2001;276:7974-7984[PMID:11113129DOI:10.1074/jbc.M008650200]
257 Claas C,Wahl J,Orlicky DJ,Karaduman H,Schn?lzer M,Kempf T,Z?ller M.The tetraspanin D6.1A and its molecular partners on rat carcinoma cells.Biochem J 2005;389:99-110[PMID:15725074DOI:10.1042/BJ20041287]
258 Le Naour F,AndréM,Boucheix C,Rubinstein E.Membrane microdomains and proteomics:lessons from tetraspanin microdomains and comparison with lipid rafts.Proteomics 2006;6:6447-6454[PMID:17109380 DOI:10.1002/pmic.200600282]
259 Kuhn S,Koch M,Nübel T,Ladwein M,Antolovic D,Klingbeil P,Hildebrand D,Moldenhauer G,Langbein L,Franke WW,Weitz J,Z?ller M.A complex of Ep CAM,claudin-7,CD44 variant isoforms,and tetraspanins promotes colorectal cancer progression.Mol Cancer Res 2007;5:553-567[PMID:17579117 DOI:10 .1158/1541-7786.MCR-06-0384]
260 Yá?ez-MóM,Barreiro O,Gordon-Alonso M,Sala-Valdés M,Sánchez-Madrid F.Tetraspanin-enriched microdomains:a functional unit in cell plasma membranes.Trends Cell Biol 2009;19:434-446[PMID:19709882 DOI:10.1016/j.tcb.2009.06.004]
261 Hemler ME.Tetraspanin proteins mediate cellular penetration,invasion,and fusion events and define a novel type of membrane microdomain.Annu Rev Cell Dev Biol 2003;19:397-422[PMID:14570575 DOI:10.1146/annurev.cellbio.19.111301.153609]
262 Andreu Z,Yá?ez-MóM.Tetraspanins in extracellular vesicle formation and function.Front Immunol 2014;5:442[PMID:25278937 DOI:10.3389/fimmu.2014.00442]
263 Scheffer KD,Gawlitza A,Spoden GA,Zhang XA,Lambert C,Berditchevski F,Florin L.Tetraspanin CD151 mediates papillomavirus type 16 endocytosis.J Virol 2013;87:3435-3446[PMID:23302890 DOI:10.1128/JVI.02906-12]
264 Stipp CS.Laminin-binding integrins and their tetraspanin partners as potential antimetastatic targets.Expert Rev Mol Med 2010;12:e3[PMID:20078909 DOI:10.1017/S1462399409001355]
265 Klinovska K,Sebkova N,Dvorakova-Hortova K.Sperm-egg fusion:a molecular enigma of mammalian reproduction.Int J Mol Sci 2014;15:10652-10668[PMID:24933635 DOI:10.3390/ijms150610652]
266 Monk PN,Partridge LJ.Tetraspanins:gateways for infection.Infect Disord Drug Targets 2012;12:4-17[PMID:22034932 DOI:10 .2174/187152612798994957]
267 Thali M.The roles of tetraspanins in HIV-1 replication.Curr Top Microbiol Immunol 2009;339:85-102[PMID:20012525 DOI:10 .1007/978-3-642-02175-6_5]
268 Zhang XA,Huang C.Tetraspanins and cell membrane tubular structures.Cell Mol Life Sci 2012;69:2843-2852[PMID:22450717 DOI:10.1007/s00018-012-0954-0]
269 Conley SM,Stuck MW,Naash MI.Structural and functional relationships between photoreceptor tetraspanins and other superfamily members.Cell Mol Life Sci 2012;69:1035-1047[PMID:21655915 DOI:10.1007/s00018-011-0736-0]
270 Greco C,Bralet MP,Ailane N,Dubart-Kupperschmitt A,Rubinstein E,Le Naour F,Boucheix C.E-cadherin/p120-catenin and tetraspanin Co-029 cooperate for cell motility control in human colon carcinoma.Cancer Res 2010;70:7674-7683[PMID:20858717 DOI:10.1158/0008-5472.CAN-09-4482]
271 Apostolou P,Toloudi M,Ioannou E,Kourtidou E,Chatziioannou M,Kopic A,Komiotis D,Kiritsis C,Manta S,Papasotiriou I.Study of the interaction among Notch pathway receptors,correlation with stemness,as well as their interaction with CD44,dipeptidyl peptidase-IV,hepatocyte growth factor receptor and the SETMAR transferase,in colon cancer stem cells.J Recept Signal Transduct Res 2013;33:353-358[PMID:23964856 DOI:10.3109/10799893.2013.828072]
272 Palagani V,El Khatib M,Kossatz U,Bozko P,Müller MR,Manns MP,Krech T,Malek NP,Plentz RR.Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/Ep CAM+cells are inhibited byγ-secretase inhibitor IX.PLo S One 2012;7:e46514[PMID:23094026 DOI:10.1371/journal.pone.0046514]
273 Philip R,Heiler S,Mu W,Büchler MW,Z?ller M,Thuma F.Claudin-7 promotes the epithelial-mesenchymal transition in human colorectal cancer.Oncotarget 2015;6:2046-2063[PMID:25514462 DOI:10.18632/oncotarget.2858]
274 Sadej R,Grudowska A,Turczyk L,Kordek R,Romanska HM.CD151 in cancer progression and metastasis:a complex scenario.Lab Invest 2014;94:41-51[PMID:24247563 DOI:10.1038/labinvest.2013.136]
275 Ashman L,Z?ller M.Tetraspanin and metastasis.In:Berditchewski F,Rubinstein E,editors.Tetraspanins.Berlin:Springer Verlag,2013:257-298
276 Cruz-Monserrate Z,O’Connor KL.Integrin alpha 6 beta 4promotes migration,invasion through Tiam1 upregulation,and subsequent Rac activation.Neoplasia 2008;10:408-417[PMID:18472958 DOI:10.1593/neo.07868]
277 Cruz-Monserrate Z,Qiu S,Evers BM,O’Connor KL.Upregulation and redistribution of integrin alpha6beta4 expression occurs at an early stage in pancreatic adenocarcinoma progression.Mod Pathol 2007;20:656-667[PMID:17415382 DOI:10.1038/modpathol.3800782]
278 Baril P,Gangeswaran R,Mahon PC,Caulee K,Kocher HM,Harada T,Zhu M,Kalthoff H,Crnogorac-Jurcevic T,Lemoine NR.Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death:role of the beta4 integrin and the PI3k pathway.Oncogene 2007;26:2082-2094[PMID:17043657 DOI:10.1038/sj.onc.1210009]
279 Carpenter BL,Chen M,Knifley T,Davis KA,Harrison SM,Stewart RL,O’Connor KL.Integrinα6β4 Promotes Autocrine Epidermal Growth Factor Receptor(EGFR)Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor(HGF).J Biol Chem 2015;290:27228-27238[PMID:26381405 DOI:10 .1074/jbc.M115.686873]
280 Laval S,Laklai H,Fanjul M,Pucelle M,Laurell H,Billon-Galés A,Le Guellec S,Delisle MB,Sonnenberg A,Susini C,Pyronnet S,Bousquet C.Dual roles of hemidesmosomal proteins in the pancreatic epithelium:the phosphoinositide 3-kinase decides.Oncogene 2014;33:1934-1944[PMID:23624916 DOI:10.1038/onc.2013.146]
281 Giancotti FG.Signal transduction by the alpha 6 beta 4 integrin:charting the path between laminin binding and nuclear events.J Cell Sci 1996;109(Pt 6):1165-1172[PMID:8799807]
282 Yang XH,Flores LM,Li Q,Zhou P,Xu F,Krop IE,Hemler ME.Disruption of laminin-integrin-CD151-focal adhesion kinase axis sensitizes breast cancer cells to Erb B2 antagonists.Cancer Res2010;70:2256-2263[PMID:20197472 DOI:10.1158/0008-5472.CAN-09-4032]
283 Lipscomb EA,Mercurio AM.Mobilization and activation of a signaling competent alpha6beta4integrin underlies its contribution to carcinoma progression.Cancer Metastasis Rev 2005;24:413-423[PMID:16258729]
284 Gagnoux-Palacios L,Dans M,van’t Hof W,Mariotti A,Pepe A,Meneguzzi G,Resh MD,Giancotti FG.Compartmentalization of integrin alpha6beta4 signaling in lipid rafts.J Cell Biol 2003;162:1189-1196[PMID:14517202 DOI:10.1083/jcb.200305006]
285 Yang X,Kovalenko OV,Tang W,Claas C,Stipp CS,Hemler ME.Palmitoylation supports assembly and function of integrintetraspanin complexes.J Cell Biol 2004;167:1231-1240[PMID:15611341 DOI:10.1083/jcb.200404100]
286 Sharma C,Rabinovitz I,Hemler ME.Palmitoylation by DHHC3is critical for the function,expression,and stability of integrinα6β4.Cell Mol Life Sci 2012;69:2233-2244[PMID:22314500DOI:10.1007/s00018-012-0924-6]
287 Germain EC,Santos TM,Rabinovitz I.Phosphorylation of a novel site on the{beta}4 integrin at the trailing edge of migrating cells promotes hemidesmosome disassembly.Mol Biol Cell 2009;20:56-67[PMID:19005215 DOI:10.1091/mbc.E08-06-0646]
288 Frijns E,Sachs N,Kreft M,Wilhelmsen K,Sonnenberg A.EGFinduced MAPK signaling inhibits hemidesmosome formation through phosphorylation of the integrin{beta}4.J Biol Chem2010;285:37650-37662[PMID:20870721 DOI:10.1074/jbc.M110.138818]
289 O’Connor KL,Chen M,Towers LN.Integrinα6β4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated Rho A activation.Am J Physiol Cell Physiol 2012;302:C605-C614[PMID:22049212 DOI:10.1152/ajpcell.00095.2011]
290 Stewart RL,O’Connor KL.Clinical significance of the integrinα6β4 in human malignancies.Lab Invest 2015;95:976-986[PMID:26121317 DOI:10.1038/labinvest.2015.82]
291 Wang H,Leavitt L,Ramaswamy R,Rapraeger AC.Interaction of syndecan and alpha6beta4 integrin cytoplasmic domains:regulation of Erb B2-mediated integrin activation.J Biol Chem2010;285:13569-13579[PMID:20181947 DOI:10.1074/jbc.M110.102137]
292 Chung J,Yoon SO,Lipscomb EA,Mercurio AM.The Met receptor and alpha 6 beta 4 integrin can function independently to promote carcinoma invasion.J Biol Chem 2004;279:32287-32293[PMID:15161909 DOI:10.1074/jbc.M403809200]
293 Wang H,Jin H,Beauvais DM,Rapraeger AC.Cytoplasmic domain interactions of syndecan-1 and syndecan-4 withα6β4integrin mediate human epidermal growth factor receptor(HER1and HER2)-dependent motility and survival.J Biol Chem2014;289:30318-30332[PMID:25202019 DOI:10.1074/jbc.M114.586438]
294 Folgiero V,Avetrani P,Bon G,Di Carlo SE,Fabi A,NisticòC,Vici P,Melucci E,Buglioni S,Perracchio L,Sperduti I,RosanòL,Sacchi A,Mottolese M,Falcioni R.Induction of Erb B-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas.PLo S One 2008;3:e1592[PMID:18270579 DOI:10.1371/journal.pone.0001592]
295 Sugiyama H,Mizutani K,Kurita S,Okimoto N,Shimono Y,Takai Y.Interaction of Necl-4/CADM4 with Erb B3 and integrinα6β4and inhibition of Erb B2/Erb B3 signaling and hemidesmosome disassembly.Genes Cells 2013;18:519-528[PMID:23611113DOI:10.1111/gtc.12056]
296 Deng X,Li Q,Hoff J,Novak M,Yang H,Jin H,Erfani SF,Sharma C,Zhou P,Rabinovitz I,Sonnenberg A,Yi Y,Zhou P,Stipp CS,Kaetzel DM,Hemler ME,Yang XH.Integrin-associated CD151drives Erb B2-evoked mammary tumor onset and metastasis.Neoplasia 2012;14:678-689[PMID:22952421 DOI:10.1593/neo.12922]
297 Lipscomb EA,Simpson KJ,Lyle SR,Ring JE,Dugan AS,Mercurio AM.The alpha6beta4 integrin maintains the survival of human breast carcinoma cells in vivo.Cancer Res 2005;65:10970-10976[PMID:16322245 DOI:10.1158/0008-5472.CAN-05-2327]
298 Faure E,Garrouste F,Parat F,Monferran S,Leloup L,Pommier G,Kovacic H,Lehmann M.P2Y2 receptor inhibits EGF-induced MAPK pathway to stabilise keratinocyte hemidesmosomes.J Cell Sci 2012;125:4264-4277[PMID:22718344 DOI:10.1242/jcs.097600]
299 Bhatia V,Mula RV,Weigel NL,Falzon M.Parathyroid hormonerelated protein regulates cell survival pathways via integrin alpha6beta4-mediated activation of phosphatidylinositol 3-kinase/Akt signaling.Mol Cancer Res 2009;7:1119-1131[PMID:19584267 DOI:10.1158/1541-7786.MCR-08-0568]
300 Mercurio AM,Bachelder RE,Bates RC,Chung J.Autocrine signaling in carcinoma:VEGF and the alpha6beta4 integrin.Semin Cancer Biol 2004;14:115-122[PMID:15018895 DOI:10.1016/j.semcancer.2003.09.016]
301 Serini G,Valdembri D,Bussolino F.Integrins and angiogenesis:a sticky business.Exp Cell Res 2006;312:651-658[PMID:16325811 DOI:10.1016/j.yexcr.2005.10.020]
302 Chen M,Sinha M,Luxon BA,Bresnick AR,O’Connor KL.Integrin alpha6beta4 controls the expression of genes associated with cell motility,invasion,and metastasis,including S100A4/metastasin.J Biol Chem 2009;284:1484-1494[PMID:19011242DOI:10.1074/jbc.M803997200]
303 Soung YH,Gil HJ,Clifford JL,Chung J.Role ofα6β4 integrin in cell motility,invasion and metastasis of mammary tumors.Curr Protein Pept Sci 2011;12:23-29[PMID:21190525 DOI:10.2174/138920311795659399]
304 Vieira AF,Ribeiro AS,Dionísio MR,Sousa B,Nobre AR,Albergaria A,Santiago-Gómez A,Mendes N,Gerhard R,Schmitt F,Clarke RB,Paredes J.P-cadherin signals through the laminin receptorα6β4 integrin to induce stem cell and invasive properties in basal-like breast cancer cells.Oncotarget 2014;5:679-692[PMID:24553076 DOI:10.18632/oncotarget.1459]
305 Wicha MS.B4 androgen ablation:attacking the prostate cancer stem cell.J Clin Invest 2013;123:563-565[PMID:23348735DOI:10.1172/JCI67460]
306 Yin Y,Deng X,Liu Z,Baldwin LA,Lefringhouse J,Zhang J,Hoff JT,Erfani SF,Rucker EB,O’Connor K,Liu C,Wu Y,Zhou BP,Yang XH.CD151 represses mammary gland development by maintaining the niches of progenitor cells.Cell Cycle 2014;13:2707-2722[PMID:25486358 DOI:10.4161/15384101.2015.945823]
307 Ramsey DM,Mc Alpine SR.Halting metastasis through CXCR4inhibition.Bioorg Med Chem Lett 2013;23:20-25[PMID:23211868 DOI:10.1016/j.bmcl.2012.10.138]
308 Hermann PC,Huber SL,Herrler T,Aicher A,Ellwart JW,Guba M,Bruns CJ,Heeschen C.Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer.Cell Stem Cell 2007;1:313-323[PMID:18371365 DOI:10.1016/j.stem.2007.06.002]
309 Du H,Bennett D,Li L,Whitlock G,Guo Y,Collins R,Chen J,Bian Z,Hong LS,Feng S,Chen X,Chen L,Zhou R,Mao E,Peto R,Chen Z.Physical activity and sedentary leisure time and their associations with BMI,waist circumference,and percentage body fat in 0.5 million adults:the China Kadoorie Biobank study.Am J Clin Nutr 2013;97:487-496[PMID:23364014 DOI:10.3945/ajcn.112.046854]
310 Bertolini G,D’Amico L,Moro M,Landoni E,Perego P,Miceli R,Gatti L,Andriani F,Wong D,Caserini R,Tortoreto M,Milione M,Ferracini R,Mariani L,Pastorino U,Roato I,Sozzi G,Roz L.Microenvironment-Modulated Metastatic CD133+/CXCR4+/Ep CAM-Lung Cancer-Initiating Cells Sustain Tumor Dissemination and Correlate with Poor Prognosis.Cancer Res2015;75:3636-3649[PMID:26141860 DOI:10.1158/0008-5472.CAN-14-3781]
311 Nagasawa T.CXC chemokine ligand 12(CXCL12)and its receptor CXCR4.J Mol Med(Berl)2014;92:433-439[PMID:24722947 DOI:10.1007/s00109-014-1123-8]
312 Trautmann F,Cojoc M,Kurth I,Melin N,Bouchez LC,Dubrovska A,Peitzsch C.CXCR4 as biomarker for radioresistant cancer stem cells.Int J Radiat Biol 2014;90:687-699[PMID:24650104 DOI:10.3109/09553002.2014.906766]
313 Chatterjee S,Behnam Azad B,Nimmagadda S.The intricate role of CXCR4 in cancer.Adv Cancer Res 2014;124:31-82[PMID:25287686 DOI:10.1016/B978-0-12-411638-2.00002-1]
314 Shi J,Wei Y,Xia J,Wang S,Wu J,Chen F,Huang G,Chen J.CXCL12-CXCR4 contributes to the implication of bone marrow in cancer metastasis.Future Oncol 2014;10:749-759[PMID:24799056 DOI:10.2217/fon.13.193]
315 Maréchal R,Demetter P,Nagy N,Berton A,Decaestecker C,Polus M,Closset J,Devière J,Salmon I,Van Laethem JL.High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma.Br J Cancer 2009;100:1444-1451[PMID:19352387 DOI:10.1038/sj.bjc.6605020]
316 Bachet JB,Maréchal R,Demetter P,Bonnetain F,Couvelard A,Svrcek M,Bardier-Dupas A,Hammel P,Sauvanet A,Louvet C,Paye F,Rougier P,Penna C,Vaillant JC,AndréT,Closset J,Salmon I,Emile JF,Van Laethem JL.Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma.Ann Oncol 2012;23:2327-2335[PMID:22377565 DOI:10.1093/annonc/mdr617]
317 Chinni SR,Yamamoto H,Dong Z,Sabbota A,Bonfil RD,Cher ML.CXCL12/CXCR4 transactivates HER2 in lipid rafts of prostate cancer cells and promotes growth of metastatic deposits in bone.Mol Cancer Res 2008;6:446-457[PMID:18337451 DOI:10 .1158/1541-7786]
318 Ho TK,Shiwen X,Abraham D,Tsui J,Baker D.StromalCell-Derived Factor-1(SDF-1)/CXCL12 as Potential Target of Therapeutic Angiogenesis in Critical Leg Ischaemia.Cardiol R e s P r a c t 2 0 1 2;2 0 1 2:143209[PMID:22462026 DOI:10 .1155/2012/143209]
319 Arjonen A,Kaukonen R,Ivaska J.Filopodia and adhesion in cancer cell motility.Cell Adh Migr 2011;5:421-430[PMID:21975551 DOI:10.4161/cam.5.5.17723]
320 Liao Y,Hung MC.Physiological regulation of Akt activity and stability.Am J Transl Res 2010;2:19-42[PMID:20182580]
321 Mo W,Chen J,Patel A,Zhang L,Chau V,Li Y,Cho W,Lim K,Xu J,Lazar AJ,Creighton CJ,Bolshakov S,Mc Kay RM,Lev D,Le LQ,Parada LF.CXCR4/CXCL12 mediate autocrine cellcycle progression in NF1-associated malignant peripheral nerve sheath tumors.Cell 2013;152:1077-1090[PMID:23434321 DOI:10 .1016/j.cell.2013.01.053]
322 Zoughlami Y,Voermans C,Brussen K,van Dort KA,Kootstra NA,Maussang D,Smit MJ,Hordijk PL,van Hennik PB.Regulation of CXCR4 conformation by the small GTPase Rac1:implications for HIV infection.Blood 2012;119:2024-2032[PMID:22238325 DOI:10.1182/blood-2011-06-364828]
323 Drury LJ,Ziarek JJ,Gravel S,Veldkamp CT,Takekoshi T,Hwang ST,Heveker N,Volkman BF,Dwinell MB.Monomeric and dimeric CXCL12 inhibit metastasis through distinct CXCR4 interactions and signaling pathways.Proc Natl Acad Sci USA 2011;108:17655-17660[PMID:21990345 DOI:10.1073/pnas.1101133108]
324 Sotillos S,Díaz-Meco MT,Moscat J,Castelli-Gair Hombría J.Polarized subcellular localization of Jak/STAT components is required for efficient signaling.Curr Biol 2008;18:624-629[PMID:18424141 DOI:10.1016/j.cub.2008.03.055]
325 Bao W,Fu HJ,Xie QS,Wang L,Zhang R,Guo ZY,Zhao J,Meng YL,Ren XL,Wang T,Li Q,Jin BQ,Yao LB,Wang RA,Fan DM,Chen SY,Jia LT,Yang AG.HER2 interacts with CD44 to upregulate CXCR4 via epigenetic silencing of micro RNA-139 in gastric cancer cells.Gastroenterology 2011;141:2076-2087.e6[PMID:21925125 DOI:10.1053/j.gastro.2011.08.050]
326 Arnaud MP,Vallée A,Robert G,Bonneau J,Leroy C,VarinBlank N,Rio AG,Troadec MB,Galibert MD,Gandemer V.CD9,a key actor in the dissemination of lymphoblastic leukemia,modulating CXCR4-mediated migration via RAC1 signaling.Blood 2015;126:1802-1812[PMID:26320102 DOI:10.1182/blood-2015-02-628560]
327 Desterke C,Martinaud C,Guerton B,Pieri L,Bogani C,Clay D,Torossian F,Lataillade JJ,Hasselbach HC,Gisslinger H,Demory JL,Dupriez B,Boucheix C,Rubinstein E,Amsellem S,Vannucchi AM,Le Bousse-Kerdilès MC.Tetraspanin CD9participates in dysmegakaryopoiesis and stromal interactions in primary myelofibrosis.Haematologica 2015;100:757-767[PMID:25840601 DOI:10.3324/haematol.2014.118497]
328 Zhang Y,Foudi A,Geay JF,Berthebaud M,Buet D,Jarrier P,Jalil A,Vainchenker W,Louache F.Intracellular localization and constitutive endocytosis of CXCR4 in human CD34+hematopoietic progenitor cells.Stem Cells 2004;22:1015-1029[PMID:15536192 DOI:10.1634/stemcells.22-6-1015]
329 Wang X,Ding X,Nan L,Wang Y,Wang J,Yan Z,Zhang W,Sun J,Zhu W,Ni B,Dong S,Yu L.Investigation of the roles of exosomes in colorectal cancer liver metastasis.Oncol Rep 2015;33:2445-2453[PMID:25760247 DOI:10.3892/or.2015.3843]
330 Munz M,Baeuerle PA,Gires O.The emerging role of Ep CAM in cancer and stem cell signaling.Cancer Res 2009;69:5627-5629[PMID:19584271 DOI:10.1158/0008-5472.CAN-09-0654]
331 Marhaba R,Klingbeil P,Nuebel T,Nazarenko I,Buechler MW,Zoeller M.CD44 and Ep CAM:cancer-initiating cell markers.Curr Mol Med 2008;8:784-804[PMID:19075676 DOI:10.2174/156652408786733667]
332 Keysar SB,Jimeno A.More than markers:biological significance of cancer stem cell-defining molecules.Mol Cancer Ther 2010;9:2450-2457[PMID:20716638 DOI:10.1158/1535-7163.MCT-10-0530]
333 Patriarca C,Macchi RM,Marschner AK,Mellstedt H.Epithelial cell adhesion molecule expression(CD326)in cancer:a short review.Cancer Treat Rev 2012;38:68-75[PMID:21576002 DOI:10 .1016/j.ctrv.2011.04.002]
334 Gires O.Lessons from common markers of tumor-initiating cells in solid cancers.Cell Mol Life Sci 2011;68:4009-4022[PMID:21786143 DOI:10.1007/s00018-011-0772-9]
335 Imrich S,Hachmeister M,Gires O.Ep CAM and its potential role in tumor-initiating cells.Cell Adh Migr 2012;6:30-38[PMID:22647938 DOI:10.4161/cam.18953]
336 DolléL,Theise ND,Schmelzer E,Boulter L,Gires O,van Grunsven LA.Ep CAM and the biology of hepatic stem/progenitor cells.Am J Physiol Gastrointest Liver Physiol 2015;308:G233-G250[PMID:25477371 DOI:10.1152/ajpgi.00069.2014]
337 Le Naour F,Zoller M.The tumor antigen Ep CAM:tetraspanins and the tight junction protein claudin-7,new partners,new functions.Front Biosci 2008;13:5847-5865[PMID:18508627]
338 Ladwein M,Pape UF,Schmidt DS,Schn?lzer M,Fiedler S,Langbein L,Franke WW,Moldenhauer G,Z?ller M.The cellcell adhesion molecule Ep CAM interacts directly with the tight junction protein claudin-7.Exp Cell Res 2005;309:345-357[PMID:16054130 DOI:10.1016/j.yexcr.2005.06.013]
339 Wu CJ,Mannan P,Lu M,Udey MC.Epithelial cell adhesion molecule(Ep CAM)regulates claudin dynamics and tight junctions.J Biol Chem 2013;288:12253-12268[PMID:23486470 DOI:10 .1074/jbc.M113.457499]
340 Okada T,Nakamura T,Watanabe T,Onoda N,Ashida A,Okuyama R,Ito K.Coexpression of Ep CAM,CD44 variant isoforms and claudin-7 in anaplastic thyroid carcinoma.PLo S One 2014;9:e94487[PMID:24727741 DOI:10.1371/journal.pone.0094487]
341 Thuma F,Z?ller M.Ep CAM-associated claudin-7 supports lymphatic spread and drug resistance in rat pancreatic cancer.Int J Cancer 2013;133:855-866[PMID:23390083 DOI:10.1002/ijc.28085]
342 Balzar M,Briaire-de Bruijn IH,Rees-Bakker HA,Prins FA,Helfrich W,de Leij L,Riethmüller G,Alberti S,Warnaar SO,Fleuren GJ,Litvinov SV.Epidermal growth factor-like repeats mediate lateral and reciprocal interactions of Ep-CAM molecules in homophilic adhesions.Mol Cell Biol 2001;21:2570-2580[PMID:11259604 DOI:10.1128/MCB.21.7.2570-2580.2001]
343 Winter MJ,Nagelkerken B,Mertens AE,Rees-Bakker HA,Briaire-de Bruijn IH,Litvinov SV.Expression of Ep-CAM shifts the state of cadherin-mediated adhesions from strong to weak.Exp Cell Res 2003;285:50-58[PMID:12681286 DOI:10.1016/S0014-4827(02)00045-9]
344 Yamashita T,Budhu A,Forgues M,Wang XW.Activation of hepatic stem cell marker Ep CAM by Wnt-beta-catenin signaling in hepatocellular carcinoma.Cancer Res 2007;67:10831-10839[PMID:18006828 DOI:10.1158/0008-5472.CAN-07-0908]
345 Lu H,Ma J,Yang Y,Shi W,Luo L.Ep CAM is an endodermspecific Wnt derepressor that licenses hepatic development.Dev Cell 2013;24:543-553[PMID:23484855 DOI:10.1016/j.devcel.2013.01.021]
346 Maghzal N,Vogt E,Reintsch W,Fraser JS,Fagotto F.The tumorassociated Ep CAM regulates morphogenetic movements through intracellular signaling.J Cell Biol 2010;191:645-659[PMID:20974811 DOI:10.1083/jcb.201004074]
347 Denzel S,Mack B,Eggert C,Massoner P,St?cklein N,Kemming D,Harréus U,Gires O.MMP7 is a target of the tumour-associated antigen Ep CAM.Int J Exp Pathol 2012;93:341-353[PMID:22974215 DOI:10.1111/j.1365-2613.2012.00826.x]
348 Sankpal NV,Willman MW,Fleming TP,Mayfield JD,Gillanders WE.Transcriptional repression of epithelial cell adhesion molecule contributes to p53 control of breast cancer invasion.Cancer Res2009;69:753-757[PMID:19141643 DOI:10.1158/0008-5472.CAN-08-2708]
349 Maetzel D,Denzel S,Mack B,Canis M,Went P,Benk M,Kieu C,Papior P,Baeuerle PA,Munz M,Gires O.Nuclear signalling by tumour-associated antigen Ep CAM.Nat Cell Biol 2009;11:162-171[PMID:19136966 DOI:10.1038/ncb1824]
350 Lin CW,Liao MY,Lin WW,Wang YP,Lu TY,Wu HC.Epithelial cell adhesion molecule regulates tumor initiation and tumorigenesis via activating reprogramming factors and epithelial-mesenchymal transition gene expression in colon cancer.J Biol Chem 2012;287:39449-39459[PMID:22989882 DOI:10.1074/jbc.M112.386235]
351 Yovchev MI,Grozdanov PN,Zhou H,Racherla H,Guha C,Dabeva MD.Identification of adult hepatic progenitor cells capable of repopulating injured rat liver.Hepatology 2008;47:636-647[PMID:18023068 DOI:10.1002/hep.22047]
352 Lei Z,Maeda T,Tamura A,Nakamura T,Yamazaki Y,Shiratori H,Yashiro K,Tsukita S,Hamada H.Ep CAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins.Dev Biol 2012;371:136-145[PMID:22819673DOI:10.1016/j.ydbio.2012.07.005]
353 Schneeberger EE,Lynch RD.The tight junction:a multifunctional complex.Am J Physiol Cell Physiol 2004;286:C1213-C1228[PMID:15151915 DOI:10.1152/ajpcell.00558.2003]
354 Lal-Nag M,Morin PJ.The claudins.Genome Biol 2009;10:235[PMID:19706201 DOI:10.1186/gb-2009-10-8-235]
355 Krug SM,Schulzke JD,Fromm M.Tight junction,selective permeability,and related diseases.Semin Cell Dev Biol 2014;36:166-176[PMID:25220018 DOI:10.1016/j.semcdb.2014.09.002]
356 Ding L,Lu Z,Foreman O,Tatum R,Lu Q,Renegar R,Cao J,Chen YH.Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice.Gastroenterology 2012;142:305-315[PMID:22044670 DOI:10.1053/j.gastro.2011.10.025]
357 Tanaka H,Takechi M,Kiyonari H,Shioi G,Tamura A,Tsukita S.Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice.Gut 2015;64:1529-1538[PMID:25691495 DOI:10.1136/gutjnl-2014-308419]
358 Van Itallie CM,Anderson JM.Claudin interactions in and out of the tight junction.Tissue Barriers 2013;1:e25247[PMID:24665401 DOI:10.4161/tisb.25247]
359 Findley MK,Koval M.Regulation and roles for claudin-family tight junction proteins.IUBMB Life 2009;61:431-437[PMID:19319969 DOI:10.1002/iub.175]
360 Gonzalez-Mariscal L,Namorado Mdel C,Martin D,Sierra G,Reyes JL.The tight junction proteins claudin-7 and-8 display a different subcellular localization at Henle’s loops and collecting ducts of rabbit kidney.Nephrol Dial Transplant 2006;21:2391-2398[PMID:16766545 DOI:10.1093/ndt/gfl255]
361 Tauro BJ,Greening DW,Mathias RA,Mathivanan S,Ji H,Simpson RJ.Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids.Mol Cell Proteomics 2013;12:587-598[PMID:23230278 DOI:10.1074/mcp.M112.021303]
362 Lu Z,Kim do H,Fan J,Lu Q,Verbanac K,Ding L,Renegar R,Chen YH.A non-tight junction function of claudin-7-Interaction with integrin signaling in suppressing lung cancer cell proliferation and detachment.Mol Cancer 2015;14:120[PMID:26081244DOI:10.1186/s12943-015-0387-0]
363 D’Souza T,Agarwal R,Morin PJ.Phosphorylation of claudin-3at threonine 192 by c AMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells.J Biol Chem2005;280:26233-26240[PMID:15905176 DOI:10.1074/jbc.M502003200]
364 French AD,Fiori JL,Camilli TC,Leotlela PD,O’Connell MP,Frank BP,Subaran S,Indig FE,Taub DD,Weeraratna AT.PKC and PKA phosphorylation affect the subcellular localization of claudin-1 in melanoma cells.Int J Med Sci 2009;6:93-101[PMID:19305641 DOI:10.7150/ijms.6.93]
365 Chen C,Wang P,Su Q,Wang S,Wang F.Myosin light chain kinase mediates intestinal barrier disruption following burn injury.PLo S One 2012;7:e34946[PMID:22529961 DOI:10.1371/journal.pone.0034946]
366 Nishida M,Yoshida M,Nishiumi S,Furuse M,Azuma T.Claudin-2 regulates colorectal inflammation via myosin light chain kinase-dependent signaling.Dig Dis Sci 2013;58:1546-1559[PMID:23306855 DOI:10.1007/s10620-012-2535-3]
367 Ikari A,Ito M,Okude C,Sawada H,Harada H,Degawa M,Sakai H,Takahashi T,Sugatani J,Miwa M.Claudin-16 is directly phosphorylated by protein kinase A independently of a vasodilatorstimulated phosphoprotein-mediated pathway.J Cell Physiol 2008;214:221-229[PMID:17559069 DOI:10.1002/jcp.21178]
368 Li X,Akhtar S,Choudhry MA.Alteration in intestine tight junction protein phosphorylation and apoptosis is associated with increase in IL-18 levels following alcohol intoxication and burn injury.Biochim Biophys Acta 2012;1822:196-203[PMID:22001439DOI:10.1016/j.bbadis.2011.09.019]
369 Shen L.Tight junctions on the move:molecular mechanisms for epithelial barrier regulation.Ann N Y Acad Sci 2012;1258:9-18[PMID:22731710 DOI:10.1111/j.1749-6632.2012.06613.x]
370 Sj?A,Magnusson KE,Peterson KH.Protein kinase C activation has distinct effects on the localization,phosphorylation and detergent solubility of the claudin protein family in tight and leaky epithelial cells.J Membr Biol 2010;236:181-189[PMID:20697888 DOI:10.1007/s00232-010-9289-7]
371 Heiler S,Mu W,Z?ller M,Thuma F.The importance of claudin-7palmitoylation on membrane subdomain localization and metastasis-promoting activities.Cell Commun Signal 2015;13:29[PMID:26054340 DOI:10.1186/s12964-015-0105-y]
372 Nübel T,Preobraschenski J,Tuncay H,Weiss T,Kuhn S,Ladwein M,Langbein L,Z?ller M.Claudin-7 regulates Ep CAM-mediated functions in tumor progression.Mol Cancer Res 2009;7:285-299[PMID:19276185 DOI:10.1158/1541-7786.MCR-08-0200]
373 Levental I,Grzybek M,Simons K.Greasing their way:lipid modifications determine protein association with membrane rafts.Biochemistry 2010;49:6305-6316[PMID:20583817 DOI:10 .1021/bi100882y]
374 Stepanek O,Draber P,Horejsi V.Palmitoylated transmembrane adaptor proteins in leukocyte signaling.Cell Signal 2014;26:895-902[PMID:24440308 DOI:10.1016/j.cellsig.2014.01.007]
375 Head BP,Patel HH,Insel PA.Interaction of membrane/lipid rafts with the cytoskeleton:impact on signaling and function:membrane/lipid rafts,mediators of cytoskeletal arrangement and cell signaling.Biochim Biophys Acta 2014;1838:532-545[PMID:23899502 DOI:10.1016/j.bbamem.2013.07.018]
376 Mollinedo F,Gajate C.Lipid rafts as major platforms for signaling regulation in cancer.Adv Biol Regul 2015;57:130-146[PMID:25465296 DOI:10.1016/j.jbior.2014.10.003]
377 Thiel KW,Carpenter G.Erb B-4 and TNF-alpha converting enzyme localization to membrane microdomains.Biochem Biophys Res Commun 2006;350:629-633[PMID:17027649 DOI:10 .1016/j.bbrc.2006.09.095]
378 Vetrivel KS,Cheng H,Kim SH,Chen Y,Barnes NY,Parent AT,Sisodia SS,Thinakaran G.Spatial segregation of gamma-secretase and substrates in distinct membrane domains.J Biol Chem2005;280:25892-25900[PMID:15886206 DOI:10.1074/jbc.M503570200]
379 Cheng JM,Volk L,Janaki DK,Vyakaranam S,Ran S,Rao KA.Tumor suppressor function of Rab25 in triple-negative breast cancer.Int J Cancer 2010;126:2799-2812[PMID:19795443DOI:10.1002/ijc.24900]
380 Nicolson GL.Cell membrane fluid-mosaic structure and cancer metastasis.Cancer Res 2015;75:1169-1176[PMID:25788696DOI:10.1158/0008-5472.CAN-14-3216]
381 Ren F,Sheng WQ,Du X.CD133:a cancer stem cells marker,is used in colorectal cancers.World J Gastroenterol 2013;19:2603-2611[PMID:23674867 DOI:10.3748/wjg.v19.i17.2603]
382 Grosse-Gehling P,Fargeas CA,Dittfeld C,Garbe Y,Alison MR,Corbeil D,Kunz-Schughart LA.CD133 as a biomarker for putative cancer stem cells in solid tumours:limitations,problems and challenges.J Pathol 2013;229:355-378[PMID:22899341 DOI:10 .1002/path.4086]
383 Yiming L,Yunshan G,Bo M,Yu Z,Tao W,Gengfang L,Dexian F,Shiqian C,Jianli J,Juan T,Zhinan C.CD133 overexpression correlates with clinicopathological features of gastric cancer patients and its impact on survival:a systematic review and metaanalysis.Oncotarget 2015;6:42019-42027[PMID:26503471DOI:10.18632/oncotarget.5714]
384 Wu Y,Wu PY.CD133 as a marker for cancer stem cells:progresses and concerns.Stem Cells Dev 2009;18:1127-1134[PMID:19409053 DOI:10.1089/scd.2008.0338]
385 Li X,Zhao H,Gu J,Zheng L.Prognostic value of cancer stem cell marker CD133 expression in pancreatic ductal adenocarcinoma(PDAC):a systematic review and meta-analysis.Int J Clin Exp Pathol 2015;8:12084-12092[PMID:26722393]
386 Xu L.Cancer stem cell in the progression and therapy of pancreatic cancer.Front Biosci(Landmark Ed)2013;18:795-802[PMID:23747847]
387 Zhu H,Wang D,Zhang L,Xie X,Wu Y,Liu Y,Shao G,Su Z.Upregulation of autophagy by hypoxia-inducible factor-1αpromotes EMT and metastatic ability of CD133+pancreatic cancer stem-like cells during intermittent hypoxia.Oncol Rep 2014;32:935-942[PMID:24994549 DOI:10.3892/or.2014.3298]
388 Hou YC,Chao YJ,Tung HL,Wang HC,Shan YS.Coexpression of CD44-positive/CD133-positive cancer stem cells and CD204-positive tumor-associated macrophages is a predictor of survival in pancreatic ductal adenocarcinoma.Cancer 2014;120:2766-2777[PMID:24839953 DOI:10.1002/cncr.28774]
389 Banerjee S,Nomura A,Sangwan V,Chugh R,Dudeja V,Vickers SM,Saluja A.CD133+tumor initiating cells in a syngenic murine model of pancreatic cancer respond to Minnelide.Clin Cancer Res2014;20:2388-2399[PMID:24634377 DOI:10.1158/1078-0432.CCR-13-2947]
390 Olempska M,Eisenach PA,Ammerpohl O,Ungefroren H,Fandrich F,Kalthoff H.Detection of tumor stem cell markers in pancreatic carcinoma cell lines.Hepatobiliary Pancreat Dis Int2007;6:92-97[PMID:17287174]
391 Yin AH,Miraglia S,Zanjani ED,Almeida-Porada G,Ogawa M,Leary AG,Olweus J,Kearney J,Buck DW.AC133,a novel marker for human hematopoietic stem and progenitor cells.Blood 1997;90:5002-5012[PMID:9389720]
392 Weigmann A,Corbeil D,Hellwig A,Huttner WB.Prominin,a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells,is targeted to plasmalemmal protrusions of non-epithelial cells.Proc Natl Acad Sci USA 1997;94:12425-12430[PMID:9356465]
393 Liu J,Mao Z,Huang J,Xie S,Liu T,Mao Z.Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy.Biochem Biophys Res Commun 2014;444:670-675[PMID:24502949 DOI:10.1016/j.bbrc.2014.01.164]
394 Liu YP,Yang CJ,Huang MS,Yeh CT,Wu AT,Lee YC,Lai TC,Lee CH,Hsiao YW,Lu J,Shen CN,Lu PJ,Hsiao M.Cisplatin selects for multidrug-resistant CD133+cells in lung adenocarcinoma by activating Notch signaling.Cancer Res2013;73:406-416[PMID:23135908 DOI:10.1158/0008-5472.CAN-12-1733]
395 Jeng KS,Sheen IS,Jeng WJ,Yu MC,Hsiau HI,Chang FY,Tsai HH.Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1-6 cells.Onco Targets Ther 2013;6:1047-1055[PMID:23950652 DOI:10 .2147/OTT.S44828]
396 Ma S.Biology and clinical implications of CD133(+)liver cancer stem cells.Exp Cell Res 2013;319:126-132[PMID:22999864DOI:10.1016/j.yexcr.2012.09.007]
397 Fargeas CA,KarbanováJ,Jászai J,Corbeil D.CD133 and membrane microdomains:old facets for future hypotheses.World J Gastroenterol 2011;17:4149-4152[PMID:22039332 DOI:10 .3748/wjg.v17.i36.4149]
398 Jiang W,Zhang Y,Kane KT,Collins MA,Simeone DM,di Magliano MP,Nguyen KT.CD44 regulates pancreatic cancer invasion through MT1-MMP.Mol Cancer Res 2015;13:9-15[PMID:25566991 DOI:10.1158/1541-7786.MCR-14-0076]
399 Preca BT,Bajdak K,Mock K,Sundararajan V,Pfannstiel J,Maurer J,Wellner U,Hopt UT,Brummer T,Brabletz S,Brabletz T,Stemmler MP.A self-enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells.Int J Cancer 2015;137:2566-2577[PMID:26077342 DOI:10.1002/ijc.29642]
400 Chanmee T,Ontong P,Mochizuki N,Kongtawelert P,Konno K,Itano N.Excessive hyaluronan production promotes acquisition of cancer stem cell signatures through the coordinated regulation of Twist and the transforming growth factorβ(TGF-β)-Snail signaling axis.J Biol Chem 2014;289:26038-26056[PMID:25077968 DOI:10.1074/jbc.M114.564120]
401 Chung SS,Aroh C,Vadgama JV.Constitutive activation of STAT3signaling regulates h TERT and promotes stem cell-like traits in human breast cancer cells.PLo S One 2013;8:e83971[PMID:24386318 DOI:10.1371/journal.pone.0083971]
402 Bao B,Wang Z,Ali S,Kong D,Li Y,Ahmad A,Banerjee S,Azmi AS,Miele L,Sarkar FH.Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells.Cancer Lett 2011;307:26-36[PMID:21463919 DOI:10 .1016/j.canlet.2011.03.012]
403 De Falco V,Tamburrino A,Ventre S,Castellone MD,Malek M,ManiéSN,Santoro M.CD44 proteolysis increases CREB phosphorylation and sustains proliferation of thyroid cancer cells.Cancer Res 2012;72:1449-1458[PMID:22271686 DOI:10 .1158/0008-5472.CAN-11-3320]
404 Lee D,Na J,Ryu J,Kim HJ,Nam SH,Kang M,Jung JW,Lee MS,Song HE,Choi J,Lee GH,Kim TY,Chung JK,Park KH,Kim SH,Kim H,Seo H,Kim P,Youn H,Lee JW.Interaction of tetraspan(in)TM4SF5 with CD44 promotes self-renewal and circulating capacities of hepatocarcinoma cells.Hepatology 2015;61:1978-1997[PMID:25627085 DOI:10.1002/hep.27721]
405 Ju SY,Chiou SH,Su Y.Maintenance of the stemness in CD44(+)HCT-15 and HCT-116 human colon cancer cells requires mi R-203suppression.Stem Cell Res 2014;12:86-100[PMID:24145190DOI:10.1016/j.scr.2013.09.011]
406 S u Y J,Lai HM,Chang YW,Chen GY,Lee JL.Direct reprogramming of stem cell properties in colon cancer cells by CD44.EMBO J 2011;30:3186-3199[PMID:21701559 DOI:10 .1038/emboj.2011.211]
407 Kang M,Choi S,Jeong SJ,Lee SA,Kwak TK,Kim H,Jung O,Lee MS,Ko Y,Ryu J,Choi YJ,Jeong D,Lee HJ,Ye SK,Kim SH,Lee JW.Cross-talk between TGFβ1 and EGFR signalling pathways induces TM4SF5 expression and epithelial-mesenchymal transition.Biochem J 2012;443:691-700[PMID:22292774 DOI:10 .1042/BJ20111584]
408 Lee SA,Lee SY,Cho IH,Oh MA,Kang ES,Kim YB,Seo WD,Choi S,Nam JO,Tamamori-Adachi M,Kitajima S,Ye SK,Kim S,Hwang YJ,Kim IS,Park KH,Lee JW.Tetraspanin TM4SF5mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma.J Clin Invest 2008;118:1354-1366[PMID:18357344 DOI:10.1172/JCI33768]
409 Lee KH,Ahn EJ,Oh SJ,Kim O,Joo YE,Bae JA,Yoon S,Ryu HH,Jung S,Kim KK,Lee JH,Moon KS.KITENIN promotes glioma invasiveness and progression,associated with the induction of EMT and stemness markers.Oncotarget 2015;6:3240-3253[PMID:25605251]
410 D’Angelo RC,Liu XW,Najy AJ,Jung YS,Won J,Chai KX,Fridman R,Kim HR.TIMP-1 via TWIST1 induces EMT phenotypes in human breast epithelial cells.Mol Cancer Res2014;12:1324-1333[PMID:24895412 DOI:10.1158/1541-7786.MCR-14-0105]
411 Baldwin LA,Hoff JT,Lefringhouse J,Zhang M,Jia C,Liu Z,Erfani S,Jin H,Xu M,She QB,van Nagell JR,Wang C,Chen L,Plattner R,Kaetzel DM,Luo J,Lu M,West D,Liu C,Ueland FR,Drapkin R,Zhou BP,Yang XH.CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling.Oncotarget 2014;5:12203-12217[PMID:25356755]
412 Lupia A,Peppicelli S,Witort E,Bianchini F,Carloni V,Pimpinelli N,Urso C,Borgognoni L,Capaccioli S,Calorini L,Lulli M.CD63tetraspanin is a negative driver of epithelial-to-mesenchymal transition in human melanoma cells.J Invest Dermatol 2014;134:2947-2956[PMID:24940653 DOI:10.1038/jid.2014.258]
413 Sobolik T,Su YJ,Wells S,Ayers GD,Cook RS,Richmond A.CXCR4 drives the metastatic phenotype in breast cancer through induction of CXCR2 and activation of MEK and PI3K pathways.Mol Biol Cell 2014;25:566-582[PMID:24403602 DOI:10.1091/mbc.E13-07-0360]
414 Jung YD,Shim JW,Park SJ,Choi SH,Yang K,Heo K,Park MT.Downregulation of UHRF1 promotes EMT via inducing CXCR4in human cancer cells.Int J Oncol 2015;46:1232-1242[PMID:25572953 DOI:10.3892/ijo.2014.2813]
415 Gao J,Yan Q,Wang J,Liu S,Yang X.Epithelial-to-mesenchymal transition induced by TGF-β1 is mediated by AP1-dependent Ep CAM expression in MCF-7 cells.J Cell Physiol 2015;230:775-782[PMID:25205054 DOI:10.1002/jcp.24802]
416 Massoner P,Thomm T,Mack B,Untergasser G,Martowicz A,Bobowski K,Klocker H,Gires O,Puhr M.Ep CAM is overexpressed in local and metastatic prostate cancer,suppressed by chemotherapy and modulated by MET-associated mi RNA-200 c/205.Br J Cancer 2014;111:955-964[PMID:24992580DOI:10.1038/bjc.2014.366]
417 Bhat AA,Pope JL,Smith JJ,Ahmad R,Chen X,Washington MK,Beauchamp RD,Singh AB,Dhawan P.Claudin-7 expression induces mesenchymal to epithelial transformation(MET)to inhibit colon tumorigenesis.Oncogene 2015;34:4570-4580[PMID:25500541 DOI:10.1038/onc.2014.385]
418 Nomura A,Banerjee S,Chugh R,Dudeja V,Yamamoto M,Vickers SM,Saluja AK.CD133 initiates tumors,induces epithelialmesenchymal transition and increases metastasis in pancreatic cancer.Oncotarget 2015;6:8313-8322[PMID:25829252]
419 Yu Z,Pestell TG,Lisanti MP,Pestell RG.Cancer stem cells.Int J Biochem Cell Biol 2012;44:2144-2151[PMID:22981632 DOI:10 .1016/j.biocel.2012.08.022]
420 Mimeault M,Batra SK.Molecular biomarkers of cancer stem/progenitor cells associated with progression,metastases,and treatment resistance of aggressive cancers.Cancer Epidemiol Biomarkers Prev 2014;23:234-254[PMID:24273063 DOI:10 .1158/1055-9965.EPI-13-0785]
421 Zaravinos A.The Regulatory Role of Micro RNAs in EMT and Cancer.J Oncol 2015;2015:865816[PMID:25883654 DOI:10 .1155/2015/865816]
422 Hu Y,Tang H.Micro RNAs regulate the epithelial to mesenchymal transition(EMT)in cancer progression.Microrna 2014;3:108-117[PMID:25323025]
423 Bourguignon LY.Hyaluronan-CD44 interaction promotes micro RNA signaling and Rho GTPase activation leading to tumor progression.Small GTPases 2012;3:53-59[PMID:22714418DOI:10.4161/sgtp.19110]
424 Bourguignon LY,Wong G,Earle C,Chen L.Hyaluronan-CD44v3interaction with Oct4-Sox2-Nanog promotes mi R-302 expression leading to self-renewal,clonal formation,and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma.J Biol Chem 2012;287:32800-32824[PMID:22847005]
425 Liu F,Kong X,Lv L,Gao J.TGF-β1 acts through mi R-155 to down-regulate TP53INP1 in promoting epithelial-mesenchymal transition and cancer stem cell phenotypes.Cancer Lett 2015;359:288-298[PMID:25633840 DOI:10.1016/j.canlet.2015.01.030]
426 Ahmad A,Maitah MY,Ginnebaugh KR,Li Y,Bao B,Gadgeel SM,Sarkar FH.Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMTregulating mi RNAs.J Hematol Oncol 2013;6:77[PMID:24199791 DOI:10.1186/1756-8722-6-77]
427 Shen WW,Zeng Z,Zhu WX,Fu GH.Mi R-142-3p functions as a tumor suppressor by targeting CD133,ABCG2,and Lgr5 in colon cancer cells.J Mol Med(Berl)2013;91:989-1000[PMID:23619912 DOI:10.1007/s00109-013-1037-x]
428 Ji Q,Hao X,Zhang M,Tang W,Yang M,Li L,Xiang D,Desano JT,Bommer GT,Fan D,Fearon ER,Lawrence TS,Xu L.Micro RNA mi R-34 inhibits human pancreatic cancer tumorinitiating cells.PLo S One 2009;4:e6816[PMID:19714243 DOI:10 .1371/journal.pone.0006816]
429 Liu C,Kelnar K,Liu B,Chen X,Calhoun-Davis T,Li H,Patrawala L,Yan H,Jeter C,Honorio S,Wiggins JF,Bader AG,Fagin R,Brown D,Tang DG.The micro RNA mi R-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44.Nat Med 2011;17:211-215[PMID:21240262 DOI:10 .1038/nm.2284]
430 Garofalo M,Romano G,Di Leva G,Nuovo G,Jeon YJ,Ngankeu A,Sun J,Lovat F,Alder H,Condorelli G,Engelman JA,Ono M,Rho JK,Cascione L,Volinia S,Nephew KP,Croce CM.EGFR and MET receptor tyrosine kinase-altered micro RNA expression induces tumorigenesis and gefitinib resistance in lung cancers.Nat Med 2012;18:74-82[PMID:22157681 DOI:10.1038/nm.2577]
431 Garnier D,Magnus N,Meehan B,Kislinger T,Rak J.Qualitative changes in the proteome of extracellular vesicles accompanying cancer cell transition to mesenchymal state.Exp Cell Res2 0 1 3;319:2747-2757[PMID:23954818 DOI:10.1016/j.yexcr.2013.08.003]
432 Aga M,Bentz GL,Raffa S,Torrisi MR,Kondo S,Wakisaka N,Yoshizaki T,Pagano JS,Shackelford J.Exosomal HIF1αsupports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes.Oncogene 2014;33:4613-4622[PMID:24662828 DOI:10.1038/onc.2014.66]
433 Mu W,Rana S,Z?ller M.Host matrix modulation by tumor exosomes promotes motility and invasiveness.Neoplasia 2013;15:875-887[PMID:23908589]
434 Purushothaman A,Bandari SK,Liu J,Mobley JA,Brown EE,Sanderson RD.Fibronectin on the Surface of Myeloma Cellderived Exosomes Mediates Exosome-Cell Interactions.J Biol Chem 2016;291:1652-1663[PMID:26601950 DOI:10.1074/jbc.M115.686295]
435 Sung BH,Ketova T,Hoshino D,Zijlstra A,Weaver AM.Directional cell movement through tissues is controlled by exosome secretion.Nat Commun 2015;6:7164[PMID:25968605DOI:10.1038/ncomms8164]
436 Rieu S,Géminard C,Rabesandratana H,Sainte-Marie J,Vidal M.Exosomes released during reticulocyte maturation bind to fibronectin via integrin alpha4beta1.Eur J Biochem 2000;267:583-590[PMID:10632729]
437 Clayton A,Turkes A,Dewitt S,Steadman R,Mason MD,Hallett MB.Adhesion and signaling by B cell-derived exosomes:the role of integrins.FASEB J 2004;18:977-979[PMID:15059973]
438 Zech D,Rana S,Büchler MW,Z?ller M.Tumor-exosomes and leukocyte activation:an ambivalent crosstalk.Cell Commun Signal2012;10:37[PMID:23190502 DOI:10.1186/1478-811X-10-37]
439 Nolte-’t Hoen EN,Buschow SI,Anderton SM,Stoorvogel W,Wauben MH.Activated T cells recruit exosomes secreted by dendritic cells via LFA-1.Blood 2009;113:1977-1981[PMID:19064723 DOI:10.1182/blood-2008-08-174094]
440 Hoshino A,Costa-Silva B,Shen TL,Rodrigues G,Hashimoto A,Tesic Mark M,Molina H,Kohsaka S,Di Giannatale A,Ceder S,Singh S,Williams C,Soplop N,Uryu K,Pharmer L,King T,Bojmar L,Davies AE,Ararso Y,Zhang T,Zhang H,Hernandez J,Weiss JM,Dumont-Cole VD,Kramer K,Wexler LH,Narendran A,Schwartz GK,Healey JH,Sandstrom P,Labori KJ,Kure EH,Grandgenett PM,Hollingsworth MA,de Sousa M,Kaur S,Jain M,Mallya K,Batra SK,Jarnagin WR,Brady MS,Fodstad O,Muller V,Pantel K,Minn AJ,Bissell MJ,Garcia BA,Kang Y,Rajasekhar VK,Ghajar CM,Matei I,Peinado H,Bromberg J,Lyden D.Tumour exosome integrins determine organotropic metastasis.Nature 2015;527:329-335[PMID:26524530 DOI:10.1038/nature15756]
441 Rana S,Z?ller M.Exosome target cell selection and the importance of exosomal tetraspanins:a hypothesis.Biochem Soc Trans 2011;39:559-562[PMID:21428939 DOI:10.1042/BST0390559]
442 Van Gool SW,Vandenberghe P,de Boer M,Ceuppens JL.CD80,CD86 and CD40 provide accessory signals in a multiple-step T-cell activation model.Immunol Rev 1996;153:47-83[PMID:9010719]
443 Matzku S,Komitowski D,Mildenberger M,Z?ller M.Characterization of BSp73,a spontaneous rat tumor and its in vivo selected variants showing different metastasizing capacities.Invasion Metastasis 1983;3:109-123[PMID:6677621]
444 Tian T,Wang Y,Wang H,Zhu Z,Xiao Z.Visualizing of the cellular uptake and intracellular trafficking of exosomes by livecell microscopy.J Cell Biochem 2010;111:488-496[PMID:20533300 DOI:10.1002/jcb.22733]
445 Mulcahy LA,Pink RC,Carter DR.Routes and mechanisms of extracellular vesicle uptake.J Extracell Vesicles 2014;3:[PMID:25143819 DOI:10.3402/jev.v3.24641]
446 Taylor MJ,Lampe M,Merrifield CJ.A feedback loop between dynamin and actin recruitment during clathrin-mediated endocytosis.PLo S Biol 2012;10:e1001302[PMID:22505844DOI:10.1371/journal.pbio.1001302]
447 Parton RG,Simons K.The multiple faces of caveolae.Nat Rev Mol Cell Biol 2007;8:185-194[PMID:17318224]
448 Kerr MC,Teasdale RD.Defining macropinocytosis.Traffic 2009;10:364-371[PMID:19192253 DOI:10.1111/j.1600-0854.2009.00878.x]
449 Chernomordik LV,Kozlov MM.Mechanics of membrane fusion.Nat Struct Mol Biol 2008;15:675-683[PMID:18596814 DOI:10 .1038/nsmb.1455]
450 Ogorevc E,Kralj-Iglic V,Veranic P.The role of extracellular vesicles in phenotypic cancer transformation.Radiol Oncol 2013;47:197-205[PMID:24133383 DOI:10.2478/raon-2013-0037]
451 Belting M,Christianson HC.Role of exosomes and microvesicles in hypoxia-associated tumour development and cardiovascular disease.J Intern Med 2015;278:251-263[PMID:26153525 DOI:10 .1111/joim.12393]
452 Aharon A,Brenner B.Microparticles,thrombosis and cancer.Best Pract Res Clin Haematol 2009;22:61-69[PMID:19285273 DOI:10 .1016/j.beha.2008.11.002]
453 Rak J.Microparticles in cancer.Semin Thromb Hemost 2010;36:888-906[PMID:21049390 DOI:10.1055/s-0030-1267043]
454 Ratajczak MZ,Kucia M,Jadczyk T,Greco NJ,Wojakowski W,Tendera M,Ratajczak J.Pivotal role of paracrine effects in stem cell therapies in regenerative medicine:can we translate stem cellsecreted paracrine factors and microvesicles into better therapeutic strategies?Leukemia 2012;26:1166-1173[PMID:22182853 DOI:10 .1038/leu.2011.389]
455 Chiarini F,Lonetti A,Evangelisti C,Buontempo F,Orsini E,Evangelisti C,Cappellini A,Neri LM,Mc Cubrey JA,Martelli AM.Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment:From biology to therapeutic targeting.Biochim Biophys Acta 2016;1863:449-463[PMID:26334291DOI:10.1016/j.bbamcr.2015.08.015]
456 Filipazzi P,Bürdek M,Villa A,Rivoltini L,Huber V.Recent advances on the role of tumor exosomes in immunosuppression and disease progression.Semin Cancer Biol 2012;22:342-349[PMID:22369922 DOI:10.1016/j.semcancer.2012.02.005]
457 Kunigelis KE,Graner MW.The Dichotomy of Tumor Exosomes(TEX)in Cancer Immunity:Is It All in the Con TEXt?Vaccines(Basel)2015;3:1019-1051[PMID:26694473 DOI:10.3390/vaccines3041019]
458 Whiteside TL.Immune modulation of T-cell and NK(natural killer)cell activities by TEXs(tumour-derived exosomes).Biochem Soc Trans 2013;41:245-251[PMID:23356291 DOI:10 .1042/BST20120265]
459 Greening DW,Gopal SK,Xu R,Simpson RJ,Chen W.Exosomes and their roles in immune regulation and cancer.Semin Cell Dev Biol 2015;40:72-81[PMID:25724562 DOI:10.1016/j.semcdb.2015.02.009]
460 Bobrie A,Théry C.Exosomes and communication between tumours and the immune system:are all exosomes equal?Biochem Soc Trans 2013;41:263-267[PMID:23356294 DOI:10.1042/BST20120245]
461 Wieckowski E,Whiteside TL.Human tumor-derived vs dendritic cell-derived exosomes have distinct biologic roles and molecular profiles.Immunol Res 2006;36:247-254[PMID:17337785]
462 Taylor DD,Gercel-Taylor C.Exosomes/microvesicles:mediators of cancer-associated immunosuppressive microenvironments.Semin Immunopathol 2011;33:441-454[PMID:21688197 DOI:10 .1007/s00281-010-0234-8]
463 Gehrmann U,N?slund TI,Hiltbrunner S,Larssen P,Gabrielsson S.Harnessing the exosome-induced immune response for cancer immunotherapy.Semin Cancer Biol 2014;28:58-67[PMID:24859748 DOI:10.1016/j.semcancer.2014.05.003]
464 Claas C,Seiter S,Claas A,Savelyeva L,Schwab M,Z?ller M.Association between the rat homologue of CO-029,a metastasisassociated tetraspanin molecule and consumption coagulopathy.J Cell Biol 1998;141:267-280[PMID:9531564]
465 Ribeiro MF,Zhu H,Millard RW,Fan GC.Exosomes Function in Pro-and Anti-Angiogenesis.Curr Angiogenes 2013;2:54-59[PMID:25374792]
466 Finn NA,Searles CD.Intracellular and Extracellular mi RNAs in Regulation of Angiogenesis Signaling.Curr Angiogenes 2012;4:299-307[PMID:23914347]
467 Gai C,Carpanetto A,Deregibus MC,Camussi G.Extracellular vesicle-mediated modulation of angiogenesis.Histol Histopathol2016;31:379-391[PMID:26662176 DOI:10.14670/HH-11-708]
468 Janowska-Wieczorek A,Wysoczynski M,Kijowski J,MarquezCurtis L,Machalinski B,Ratajczak J,Ratajczak MZ.Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer.Int J Cancer 2005;113:752-760[PMID:15499615]
469 Shimoda M,Khokha R.Proteolytic factors in exosomes.Proteomics 2013;13:1624-1636[PMID:23526769 DOI:10.1002/pmic.201200458]
470 Sevenich L,Joyce JA.Pericellular proteolysis in cancer.Genes Dev2014;28:2331-2347[PMID:25367033 DOI:10.1101/gad.250647.114]
471 Stoeck A,Keller S,Riedle S,Sanderson MP,Runz S,Le Naour F,Gutwein P,Ludwig A,Rubinstein E,Altevogt P.A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44.Biochem J 2006;393:609-618[PMID:16229685]
472 Nakamura H,Suenaga N,Taniwaki K,Matsuki H,Yonezawa K,Fujii M,Okada Y,Seiki M.Constitutive and induced CD44shedding by ADAM-like proteases and membrane-type 1 matrix metalloproteinase.Cancer Res 2004;64:876-882[PMID:14871815]
473 Chetty C,Vanamala SK,Gondi CS,Dinh DH,Gujrati M,Rao JS.MMP-9 induces CD44 cleavage and CD44 mediated cell migration in glioblastoma xenograft cells.Cell Signal 2012;24:549-559[PMID:22024282 DOI:10.1016/j.cellsig.2011.10.008]
474 Tsaktanis T,Kremling H,Pav?i?M,von Stackelberg R,Mack B,Fukumori A,Steiner H,Vielmuth F,Spindler V,Huang Z,Jakubowski J,Stoecklein NH,Luxenburger E,Lauber K,Lenar?i?B,Gires O.Cleavage and cell adhesion properties of human epithelial cell adhesion molecule(HEPCAM).J Biol Chem2015;290:24574-24591[PMID:26292218 DOI:10.1074/jbc.M115.662700]
475 Lokeshwar VB,Mirza S,Jordan A.Targeting hyaluronic acid family for cancer chemoprevention and therapy.Adv Cancer Res2014;123:35-65[PMID:25081525 DOI:10.1016/B978-0-12-800092-2.00002-2]
476 Rilla K,Siiskonen H,Tammi M,Tammi R.Hyaluronan-coated extracellular vesicles--a novel link between hyaluronan and cancer.Adv Cancer Res 2014;123:121-148[PMID:25081528 DOI:10 .1016/B978-0-12-800092-2.00005-8]
477 Seiki M.Membrane-type 1 matrix metalloproteinase:a key enzyme for tumor invasion.Cancer Lett 2003;194:1-11[PMID:12706853]
478 Bauvois B.New facets of matrix metalloproteinases MMP-2and MMP-9 as cell surface transducers:outside-in signaling and relationship to tumor progression.Biochim Biophys Acta 2012;1825:29-36[PMID:22020293 DOI:10.1016/j.bbcan.2011.10.001]
479 Ramteke A,Ting H,Agarwal C,Mateen S,Somasagara R,Hussain A,Graner M,Frederick B,Agarwal R,Deep G.Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules.Mol Carcinog 2015;54:554-565[PMID:24347249 DOI:10.1002/mc.22124]
480 Tauro BJ,Mathias RA,Greening DW,Gopal SK,Ji H,Kapp EA,Coleman BM,Hill AF,Kusebauch U,Hallows JL,Shteynberg D,Moritz RL,Zhu HJ,Simpson RJ.Oncogenic H-ras reprograms Madin-Darby canine kidney(MDCK)cell-derived exosomal proteins following epithelial-mesenchymal transition.Mol Cell Proteomics 2013;12:2148-2159[PMID:23645497 DOI:10.1074/mcp.M112.027086]
481 Mazurov D,Barbashova L,Filatov A.Tetraspanin protein CD9interacts with metalloprotease CD10 and enhances its release via exosomes.FEBS J 2013;280:1200-1213[PMID:23289620 DOI:10 .1111/febs.12110]
482 Liu T,Mendes DE,Berkman CE.Functional prostate-specific membrane antigen is enriched in exosomes from prostate cancer cells.Int J Oncol 2014;44:918-922[PMID:24424840 DOI:10 .3892/ijo.2014.2256]
483 Hakulinen J,Sankkila L,Sugiyama N,Lehti K,Keski-Oja J.Secretion of active membrane type 1 matrix metalloproteinase(MMP-14)into extracellular space in microvesicular exosomes.J Cell Biochem 2008;105:1211-1218[PMID:18802920 DOI:10 .1002/jcb.21923]
484 Hendrix A,Westbroek W,Bracke M,De Wever O.An ex(o)citing machinery for invasive tumor growth.Cancer Res 2010;70:9533-9537[PMID:21098711 DOI:10.1158/0008-5472.CAN-10-3248]
485 Hood JL,San RS,Wickline SA.Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis.Cancer Res2011;71:3792-3801[PMID:21478294 DOI:10.1158/0008-5472.CAN-10-4455]
486 Peinado H,Ale?kovi?M,Lavotshkin S,Matei I,Costa-Silva B,Moreno-Bueno G,Hergueta-Redondo M,Williams C,GarcíaSantos G,Ghajar C,Nitadori-Hoshino A,Hoffman C,Badal K,Garcia BA,Callahan MK,Yuan J,Martins VR,Skog J,Kaplan RN,Brady MS,Wolchok JD,Chapman PB,Kang Y,Bromberg J,Lyden D.Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.Nat Med2012;18:883-891[PMID:22635005 DOI:10.1038/nm.2753]
487 Webber J,Yeung V,Clayton A.Extracellular vesicles as modulators of the cancer microenvironment.Semin Cell Dev Biol 2015;40:27-34[PMID:25662446 DOI:10.1016/j.semcdb.2015.01.013]
488 Altevogt P,Bretz NP,Ridinger J,Utikal J,Umansky V.Novel insights into exosome-induced,tumor-associated inflammation and immunomodulation.Semin Cancer Biol 2014;28:51-57[PMID:24769223 DOI:10.1016/j.semcancer.2014.04.008]
489 Whitehead B,Wu L,Hvam ML,Aslan H,Dong M,Dyrskj?t L,Ostenfeld MS,Moghimi SM,Howard KA.Tumour exosomes display differential mechanical and complement activation properties dependent on malignant state:implications in endothelial leakiness.J Extracell Vesicles 2015;4:29685[PMID:26714455DOI:10.3402/jev.v4.29685]
490 Fontana S,Saieva L,Taverna S,Alessandro R.Contribution of proteomics to understanding the role of tumor-derived exosomes in cancer progression:state of the art and new perspectives.Proteomics 2013;13:1581-1594[PMID:23401131 DOI:10.1002/pmic.201200398]
491 Brandt DT,Xu J,Steinbeisser H,Grosse R.Regulation of myocardin-related transcriptional coactivators through cofactor interactions in differentiation and cancer.Cell Cycle 2009;8:2523-2527[PMID:19625774]
492 Lee NP,Poon RT,Shek FH,Ng IO,Luk JM.Role of cadherin-17 in oncogenesis and potential therapeutic implications in hepatocellular carcinoma.Biochim Biophys Acta 2010;1806:138-145[PMID:20580775 DOI:10.1016/j.bbcan.2010.05.002]
493 Mathew SJ,Haubert D,Kr?nke M,Leptin M.Looking beyond death:a morphogenetic role for the TNF signalling pathway.J Cell Sci 2009;122:1939-1946[PMID:19494121 DOI:10.1242/jcs.044487]
494 Liu QS,Zhang J,Liu M,Dong WG.Lentiviral-mediated mi RNA against liver-intestine cadherin suppresses tumor growth and invasiveness of human gastric cancer.Cancer Sci 2010;101:1807-1812[PMID:20500517 DOI:10.1111/j.1349-7006.2010.01600.x]
495 Pang W,Su J,Wang Y,Feng H,Dai X,Yuan Y,Chen X,Yao W.Pancreatic cancer-secreted mi R-155 implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts.Cancer Sci2015;106:1362-1369[PMID:26195069 DOI:10.1111/cas.12747]
496 Ratajczak J,Miekus K,Kucia M,Zhang J,Reca R,Dvorak P,Ratajczak MZ.Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors:evidence for horizontal transfer of m RNA and protein delivery.Leukemia 2006;20:847-856[PMID:16453000]
497 Pan Q,Ramakrishnaiah V,Henry S,Fouraschen S,de Ruiter PE,Kwekkeboom J,Tilanus HW,Janssen HL,van der Laan LJ.Hepatic cell-to-cell transmission of small silencing RNA can extend the therapeutic reach of RNA interference(RNAi).Gut 2012;61:1330-1339[PMID:22198713 DOI:10.1136/gutjnl-2011-300449]
498 Verweij FJ,Middeldorp JM,Pegtel DM.Intracellular signaling controlled by the endosomal-exosomal pathway.Commun Integr Biol 2012;5:88-93[PMID:22482020]
499 Higginbotham JN,Demory Beckler M,Gephart JD,Franklin JL,Bogatcheva G,Kremers GJ,Piston DW,Ayers GD,Mc Connell RE,Tyska MJ,Coffey RJ.Amphiregulin exosomes increase cancer cell invasion.Curr Biol 2011;21:779-786[PMID:21514161 DOI:10 .1016/j.cub.2011.03.043]
500 Yang M,Chen J,Su F,Yu B,Su F,Lin L,Liu Y,Huang JD,Song E.Microvesicles secreted by macrophages shuttle invasionpotentiating micro RNAs into breast cancer cells.Mol Cancer 2011;10:117[PMID:21939504 DOI:10.1186/1476-4598-10-117]
501 Zhang Y,Liu D,Chen X,Li J,Li L,Bian Z,Sun F,Lu J,Yin Y,Cai X,Sun Q,Wang K,Ba Y,Wang Q,Wang D,Yang J,Liu P,Xu T,Yan Q,Zhang J,Zen K,Zhang CY.Secreted monocytic mi R-150enhances targeted endothelial cell migration.Mol Cell 2010;39:133-144[PMID:20603081 DOI:10.1016/j.molcel.2010.06.010]
502 Roninson IB.Molecular mechanism of multidrug resistance in tumor cells.Clin Physiol Biochem 1987;5:140-151[PMID:2887329]
503 Bebawy M,Combes V,Lee E,Jaiswal R,Gong J,Bonhoure A,Grau GE.Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells.Leukemia 2009;23:1643-1649[PMID:19369960 DOI:10.1038/leu.2009.76]
504 Aga M,Bradley JM,Wanchu R,Yang YF,Acott TS,Keller KE.Differential effects of caveolin-1 and-2 knockdown on aqueous outflow and altered extracellular matrix turnover in caveolin-silenced trabecular meshwork cells.Invest Ophthalmol Vis Sci 2014;55:5497-5509[PMID:25103269 DOI:10.1167/iovs.14-14519]
2 Wang Z,Lai ST,Xie L,Zhao JD,Ma NY,Zhu J,Ren ZG,Jiang GL.Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus:a systematic review and meta-analysis.Diabetes Res Clin Pract 2014;106:19-26[PMID:24837144 DOI:10.1016/j.diabres.2014.04.007]
3 Wang XY,Yang F,Jin C,Fu DL.Utility of PET/CT in diagnosis,staging,assessment of resectability and metabolic response of pancreatic cancer.World J Gastroenterol 2014;20:15580-15589[PMID:25400441 DOI:10.3748/wjg.v20.i42.15580]
4 Urayama S.Pancreatic cancer early detection:expanding higherrisk group with clinical and metabolomics parameters.World J Gastroenterol 2015;21:1707-1717[PMID:25684935 DOI:10 .3748/wjg.v21.i6.1707]
5 Del Chiaro M,Segersv?rd R,Lohr M,Verbeke C.Early detection and prevention of pancreatic cancer:is it really possible today?World J Gastroenterol 2014;20:12118-12131[PMID:25232247DOI:10.3748/wjg.v20.i34.12118]
6 Jenkinson C,Earl J,Ghaneh P,Halloran C,Carrato A,Greenhalf W,Neoptolemos J,Costello E.Biomarkers for early diagnosis of pancreatic cancer.Expert Rev Gastroenterol Hepatol 2015;9:305-315[PMID:25373768 DOI:10.1586/17474124.2015.965145]
7 Ansari D,Gustafsson A,Andersson R.Update on the management of pancreatic cancer:surgery is not enough.World J Gastroenterol2015;21:3157-3165[PMID:25805920 DOI:10.3748/wjg.v21.i11.3157]
8 Okano K,Suzuki Y.Strategies for early detection of resectable pancreatic cancer.World J Gastroenterol 2014;20:11230-11240[PMID:25170207 DOI:10.3748/wjg.v20.i32.11230]
9 He XY,Yuan YZ.Advances in pancreatic cancer research:moving towards early detection.World J Gastroenterol 2014;20:11241-11248[PMID:25170208 DOI:10.3748/wjg.v20.i32.11241]
10 Goonetilleke KS,Siriwardena AK.Systematic review of carbohydrate antigen(CA 19-9)as a biochemical marker in the diagnosis of pancreatic cancer.Eur J Surg Oncol 2007;33:266-270[PMID:17097848]
11 Bussom S,Saif MW.Methods and rationale for the early detection of pancreatic cancer.Highlights from the“2010 ASCO Gastrointestinal Cancers Symposium”.Orlando,FL,USA.January22 -24,2010.JOP 2010;11:128-130[PMID:20208319]
12 Gold DV,Modrak DE,Ying Z,Cardillo TM,Sharkey RM,Goldenberg DM.New MUC1 serum immunoassay differentiates pancreatic cancer from pancreatitis.J Clin Oncol 2006;24:252-258[PMID:16344318]
13 Canto MI,Goggins M,Yeo CJ,Griffin C,Axilbund JE,Brune K,Ali SZ,Jagannath S,Petersen GM,Fishman EK,Piantadosi S,Giardiello FM,Hruban RH.Screening for pancreatic neoplasia in high-risk individuals:an EUS-based approach.Clin Gastroenterol Hepatol 2004;2:606-621[PMID:15224285]
14 Chen Y,Kang M,Lu W,Guo Q,Zhang B,Xie Q,Wu Y.DJ-1,a novel biomarker and a selected target gene for overcoming chemoresistance in pancreatic cancer.J Cancer Res Clin Oncol 2012;138:1463-1474[PMID:22526154 DOI:10.1007/s00432-012-1205-3]
15 Makawita S,Dimitromanolakis A,Soosaipillai A,Soleas I,Chan A,Gallinger S,Haun RS,Blasutig IM,Diamandis EP.Validation of four candidate pancreatic cancer serological biomarkers that improve the performance of CA19.9.BMC Cancer 2013;13:404[PMID:24007603 DOI:10.1186/1471-2407-13-404]
16 Wingren C,Sandstr?m A,Segersv?rd R,Carlsson A,Andersson R,L?hr M,Borrebaeck CA.Identification of serum biomarker signatures associated with pancreatic cancer.Cancer Res 2012;72:2481-2490[PMID:22589272 DOI:10.1158/0008-5472.CAN-11-2883]
17 Ansari D,Andersson R,Bauden MP,Andersson B,Connolly JB,Welinder C,Sasor A,Marko-Varga G.Protein deep sequencing applied to biobank samples from patients with pancreatic cancer.J Cancer Res Clin Oncol 2015;141:369-380[PMID:25216700DOI:10.1007/s00432-014-1817-x]
18 Chen R,Yi EC,Donohoe S,Pan S,Eng J,Cooke K,Crispin DA,Lane Z,Goodlett DR,Bronner MP,Aebersold R,Brentnall TA.Pancreatic cancer proteome:the proteins that underlie invasion,metastasis,and immunologic escape.Gastroenterology 2005;129:1187-1197[PMID:16230073]
19 Lu Z,Hu L,Evers S,Chen J,Shen Y.Differential expression profiling of human pancreatic adenocarcinoma and healthy pancreatic tissue.Proteomics 2004;4:3975-3988[PMID:15526344]
20 Shen J,Person MD,Zhu J,Abbruzzese JL,Li D.Protein expression profiles in pancreatic adenocarcinoma compared with normal pancreatic tissue and tissue affected by pancreatitis as detected by two-dimensional gel electrophoresis and mass spectrometry.Cancer Res 2004;64:9018-9026[PMID:15604267]
21 Fukushige S,Horii A.Road to early detection of pancreatic cancer:Attempts to utilize epigenetic biomarkers.Cancer Lett 2014;342:231-237[PMID:22450751 DOI:10.1016/j.canlet.2012.03.022]
22 Rachagani S,Macha MA,Heimann N,Seshacharyulu P,Haridas D,Chugh S,Batra SK.Clinical implications of mi RNAs in the pathogenesis,diagnosis and therapy of pancreatic cancer.Adv Drug Deliv Rev 2015;81:16-33[PMID:25453266 DOI:10.1016/j.addr.2014.10.020]
23 Z?ller M.Pancreatic cancer diagnosis by free and exosomal mi RNA.World J Gastrointest Pathophysiol 2013;4:74-90[PMID:24340225 DOI:10.4291/wjgp.v4.i4.74]
24 Yi JM,Guzzetta AA,Bailey VJ,Downing SR,Van Neste L,Chiappinelli KB,Keeley BP,Stark A,Herrera A,Wolfgang C,Pappou EP,Iacobuzio-Donahue CA,Goggins MG,Herman JG,Wang TH,Baylin SB,Ahuja N.Novel methylation biomarker panel for the early detection of pancreatic cancer.Clin Cancer Res2013;19:6544-6555[PMID:24088737 DOI:10.1158/1078-0432.CCR-12-3224]
25 Nagpal G,Sharma M,Kumar S,Chaudhary K,Gupta S,Gautam A,Raghava GP.PCMdb:pancreatic cancer methylation database.Sci Rep 2014;4:4197[PMID:24569397 DOI:10.1038/srep04197]
26 Jin K,Luo G,Xiao Z,Liu Z,Liu C,Ji S,Xu J,Liu L,Long J,Ni Q,Yu X.Noncoding RNAs as potential biomarkers to predict the outcome in pancreatic cancer.Drug Des Devel Ther 2015;9:1247-1255[PMID:25750521 DOI:10.2147/DDDT.S77597]
27 Wang J,Chen J,Chang P,Le Blanc A,Li D,Abbruzzesse JL,Frazier ML,Killary AM,Sen S.Micro RNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease.Cancer Prev Res(Phila)2009;2:807-813[PMID:19723895 DOI:10.1158/1940-6207.CAPR-09-0094]
28 Liu J,Gao J,Du Y,Li Z,Ren Y,Gu J,Wang X,Gong Y,Wang W,Kong X.Combination of plasma micro RNAs with serum CA19-9for early detection of pancreatic cancer.Int J Cancer 2012;131:683-691[PMID:21913185 DOI:10.1002/ijc.26422]
29 Liu R,Chen X,Du Y,Yao W,Shen L,Wang C,Hu Z,Zhuang R,Ning G,Zhang C,Yuan Y,Li Z,Zen K,Ba Y,Zhang CY.Serum micro RNA expression profile as a biomarker in the diagnosis and prognosis of pancreatic cancer.Clin Chem 2012;58:610-618[PMID:22194634 DOI:10.1373/clinchem.2011.172767]
30 Schultz NA,Dehlendorff C,Jensen BV,Bjerregaard JK,Nielsen KR,Bojesen SE,Calatayud D,Nielsen SE,Yilmaz M,Holl?nder NH,Andersen KK,Johansen JS.Micro RNA biomarkers in whole blood for detection of pancreatic cancer.JAMA 2014;311:392-404[PMID:24449318 DOI:10.1001/jama.2013.284664]
31 Wan C,Shen Y,Yang T,Wang T,Chen L,Wen F.Diagnostic value of micro RNA for pancreatic cancer:a meta-analysis.Arch Med Sci 2012;8:749-755[PMID:23185182 DOI:10.5114/aoms.2012.31609]
32 Kahlert C,Melo SA,Protopopov A,Tang J,Seth S,Koch M,Zhang J,Weitz J,Chin L,Futreal A,Kalluri R.Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.J Biol Chem 2014;289:3869-3875[PMID:24398677 DOI:10.1074/jbc.C113.532267]
33 Que R,Ding G,Chen J,Cao L.Analysis of serum exosomal micro RNAs and clinicopathologic features of patients with pancreatic adenocarcinoma.World J Surg Oncol 2013;11:219[PMID:24007214 DOI:10.1186/1477-7819-11-219]
34 Melo SA,Luecke LB,Kahlert C,Fernandez AF,Gammon ST,Kaye J,Le Bleu VS,Mittendorf EA,Weitz J,Rahbari N,Reissfelder C,Pilarsky C,Fraga MF,Piwnica-Worms D,Kalluri R.Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.Nature 2015;523:177-182[PMID:26106858 DOI:10 .1038/nature14581]
35 Madhavan B,Yue S,Galli U,Rana S,Gross W,Müller M,Giese NA,Kalthoff H,Becker T,Büchler MW,Z?ller M.Combined evaluation of a panel of protein and mi RNA serum-exosome biomarkers for pancreatic cancer diagnosis increases sensitivity and specificity.Int J Cancer 2015;136:2616-2627[PMID:25388097 DOI:10.1002/ijc.29324]
36 Sohal DP,Walsh RM,Ramanathan RK,Khorana AA.Pancreatic adenocarcinoma:treating a systemic disease with systemic therapy.J Natl Cancer Inst 2014;106:dju011[PMID:24563516 DOI:10 .1093/jnci/dju011]
37 Greenow K,Clarke AR.Controlling the stem cell compartment and regeneration in vivo:the role of pluripotency pathways.Physiol Rev 2012;92:75-99[PMID:22298652 DOI:10.1152/physrev.00040.2010]
38 Sales KM,Winslet MC,Seifalian AM.Stem cells and cancer:an overview.Stem Cell Rev 2007;3:249-255[PMID:17955391]
39 Ta m W L,Weinberg RA.The epigenetics of epithelialmesenchymal plasticity in cancer.Nat Med 2013;19:1438-1449[PMID:24202396 DOI:10.1038/nm.3336]
40 Cerdan C,Bhatia M.Novel roles for Notch,Wnt and Hedgehog in hematopoesis derived from human pluripotent stem cells.Int J Dev Biol 2010;54:955-963[PMID:20336604 DOI:10.1387/ijdb.103067cc]
41 Fossett N.Signal transduction pathways,intrinsic regulators,and the control of cell fate choice.Biochim Biophys Acta 2013;1830:2375-2384[PMID:22705942 DOI:10.1016/j.bbagen.2012.06.005]
42 Brabletz T,Jung A,Spaderna S,Hlubek F,Kirchner T.Opinion:migrating cancer stem cells-an integrated concept of malignant tumour progression.Nat Rev Cancer 2005;5:744-749[PMID:16148886]
43 Thiery JP,Acloque H,Huang RY,Nieto MA.Epithelialmesenchymal transitions in development and disease.Cell 2009;139:871-890[PMID:19945376 DOI:10.1016/j.cell.2009.11.007]
44 Mani SA,Guo W,Liao MJ,Eaton EN,Ayyanan A,Zhou AY,Brooks M,Reinhard F,Zhang CC,Shipitsin M,Campbell LL,Polyak K,Brisken C,Yang J,Weinberg RA.The epithelialmesenchymal transition generates cells with properties of stem cells.Cell 2008;133:704-715[PMID:18485877 DOI:10.1016/j.cell.2008.03.027]
45 Wang Z,Ali S,Banerjee S,Bao B,Li Y,Azmi AS,Korc M,Sarkar FH.Activated K-Ras and INK4a/Arf deficiency promote aggressiveness of pancreatic cancer by induction of EMT consistent with cancer stem cell phenotype.J Cell Physiol 2013;228:556-562[PMID:22806240 DOI:10.1002/jcp.24162]
46 Biddle A,Mackenzie IC.Cancer stem cells and EMT in carcinoma.Cancer Metastasis Rev 2012;Epub ahead of print[PMID:22302111]
47 Scheel C,Eaton EN,Li SH,Chaffer CL,Reinhardt F,Kah KJ,Bell G,Guo W,Rubin J,Richardson AL,Weinberg RA.Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast.Cell 2011;145:926-940[PMID:21663795DOI:10.1016/j.cell.2011.04.029]
48 Lamouille S,Xu J,Derynck R.Molecular mechanisms of epithelial-mesenchymal transition.Nat Rev Mol Cell Biol 2014;15:178-196[PMID:24556840 DOI:10.1038/nrm3758]
49 Tania M,Khan MA,Fu J.Epithelial to mesenchymal transition inducing transcription factors and metastatic cancer.Tumour Biol2014;35:7335-7342[PMID:24880591 DOI:10.1007/s13277-014 -2163-y]
50 Moustakas A,Heldin P.TGFβand matrix-regulated epithelial to mesenchymal transition.Biochim Biophys Acta 2014;1840:2621-2634[PMID:24561266 DOI:10.1016/j.bbagen.2014.02.004]
51 Taylor MA,Parvani JG,Schiemann WP.The pathophysiology of epithelial-mesenchymal transition induced by transforming growth factor-beta in normal and malignant mammary epithelial cells.J Mammary Gland Biol Neoplasia 2010;15:169-190[PMID:20467795 DOI:10.1007/s10911-010-9181-1]
52 Reya T,Clevers H.Wnt signalling in stem cells and cancer.Nature2005;434:843-850[PMID:15829953]
53 Vermeulen L,De Sousa E Melo F,van der Heijden M,Cameron K,de Jong JH,Borovski T,Tuynman JB,Todaro M,Merz C,Rodermond H,Sprick MR,Kemper K,Richel DJ,Stassi G,Medema JP.Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.Nat Cell Biol 2010;12:468-476[PMID:20418870 DOI:10.1038/ncb2048]
54 Yook JI,Li XY,Ota I,Hu C,Kim HS,Kim NH,Cha SY,Ryu JK,Choi YJ,Kim J,Fearon ER,Weiss SJ.A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells.Nat Cell Biol 2006;8:1398-1406[PMID:17072303]
55 Brabletz S,Bajdak K,Meidhof S,Burk U,Niedermann G,Firat E,Wellner U,Dimmler A,Faller G,Schubert J,Brabletz T.The ZEB1/mi R-200 feedback loop controls Notch signalling in cancer cells.EMBO J 2011;30:770-782[PMID:21224848 DOI:10 .1038/emboj.2010.349]
56 Thomson S,Petti F,Sujka-Kwok I,Mercado P,Bean J,Monaghan M,Seymour SL,Argast GM,Epstein DM,Haley JD.A systems view of epithelial-mesenchymal transition signaling states.Clin Exp Metastasis 2011;28:137-155[PMID:21194007 DOI:10 .1007/s10585-010-9367-3]
57 Hardy KM,Booth BW,Hendrix MJ,Salomon DS,Strizzi L.Erb B/EGF signaling and EMT in mammary development and breast cancer.J Mammary Gland Biol Neoplasia 2010;15:191-199[PMID:20369376 DOI:10.1007/s10911-010-9172-2]
58 Peinado H,Olmeda D,Cano A.Snail,Zeb and b HLH factors in tumour progression:an alliance against the epithelial phenotype?Nat Rev Cancer 2007;7:415-428[PMID:17508028]
59 Cedar H,Bergman Y.Linking DNA methylation and histone modification:patterns and paradigms.Nat Rev Genet 2009;10:295-304[PMID:19308066 DOI:10.1038/nrg2540]
60 Song LB,Li J,Liao WT,Feng Y,Yu CP,Hu LJ,Kong QL,Xu LH,Zhang X,Liu WL,Li MZ,Zhang L,Kang TB,Fu LW,Huang WL,Xia YF,Tsao SW,Li M,Band V,Band H,Shi QH,Zeng YX,Zeng MS.The polycomb group protein Bmi-1 represses the tumor suppressor PTEN and induces epithelial-mesenchymal transition in human nasopharyngeal epithelial cells.J Clin Invest 2009;119:3626-3636[PMID:19884659 DOI:10.1172/JCI39374]
61 Martin A,Cano A.Tumorigenesis:Twist1 links EMT to selfrenewal.Nat Cell Biol 2010;12:924-925[PMID:20885418 DOI:10 .1038/ncb1010-924]
62 von Burstin J,Eser S,Paul MC,Seidler B,Brandl M,Messer M,von Werder A,Schmidt A,Mages J,Pagel P,Schnieke A,Schmid RM,Schneider G,Saur D.E-cadherin regulates metastasis of pancreatic cancer in vivo and is suppressed by a SNAIL/HDAC1/HDAC2 repressor complex.Gastroenterology 2009;137:361-71,371 .e1-5[PMID:19362090 DOI:10.1053/j.gastro.2009.04.004]
63 Fu J,Qin L,He T,Qin J,Hong J,Wong J,Liao L,Xu J.The TWIST/Mi2/Nu RD protein complex and its essential role in cancer metastasis.Cell Res 2011;21:275-289[PMID:20714342 DOI:10 .1038/cr.2010.118]
64 Scherr M,Eder M.Gene silencing by small regulatory RNAs in mammalian cells.Cell Cycle 2007;6:444-449[PMID:17312397]
65 Gregory PA,Bert AG,Paterson EL,Barry SC,Tsykin A,Farshid G,Vadas MA,Khew-Goodall Y,Goodall GJ.The mi R-200 family and mi R-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.Nat Cell Biol 2008;10:593-601[PMID:18376396 DOI:10.1038/ncb1722]
66 Ru P,Steele R,Newhall P,Phillips NJ,Toth K,Ray RB.mi RNA-29 b suppresses prostate cancer metastasis by regulating epithelialmesenchymal transition signaling.Mol Cancer Ther 2012;11:1166-1173[PMID:22402125 DOI:10.1158/1535-7163.MCT-12-0100]
67 Zhang J,Zhang H,Liu J,Tu X,Zang Y,Zhu J,Chen J,Dong L,Zhang J.mi R-30 inhibits TGF-β1-induced epithelial-tomesenchymal transition in hepatocyte by targeting Snail1.Biochem Biophys Res Commun 2012;417:1100-1105[PMID:22227196DOI:10.1016/j.bbrc.2011.12.121]
68 Gandellini P,Giannoni E,Casamichele A,Taddei ML,Callari M,Piovan C,Valdagni R,Pierotti MA,Zaffaroni N,Chiarugi P.mi R-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts.Antioxid Redox Signal 2014;20:1045-1059[PMID:23924028 DOI:10.1089/ars.2013.5292]
69 Ma L,Young J,Prabhala H,Pan E,Mestdagh P,Muth D,TeruyaFeldstein J,Reinhardt F,Onder TT,Valastyan S,Westermann F,Speleman F,Vandesompele J,Weinberg RA.mi R-9,a MYC/MYCN-activated micro RNA,regulates E-cadherin and cancer metastasis.Nat Cell Biol 2010;12:247-256[PMID:20173740DOI:10.1038/ncb2024]
70 Meng Z,Fu X,Chen X,Zeng S,Tian Y,Jove R,Xu R,Huang W.mi R-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice.Hepatology 2010;52:2148-2157[PMID:20979124 DOI:10.1002/hep.23915]
71 Vetter G,Saumet A,Moes M,Vallar L,Le Béchec A,Laurini C,Sabbah M,Arar K,Theillet C,Lecellier CH,Friederich E.mi R-661expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1and Star D10 messengers.Oncogene 2010;29:4436-4448[PMID:20543867 DOI:10.1038/onc.2010.181]
72 Zhou Q,Fan J,Ding X,Peng W,Yu X,Chen Y,Nie J.TGF-{beta}-induced Mi R-491-5p expression promotes Par-3degradation in rat proximal tubular epithelial cells.J Biol Chem2010;285:40019-40027[PMID:20966078 DOI:10.1074/jbc.M110.141341]
73 Hamada S,Satoh K,Miura S,Hirota M,Kanno A,Masamune A,Kikuta K,Kume K,Unno J,Egawa S,Motoi F,Unno M,Shimosegawa T.mi R-197 induces epithelial-mesenchymal transition in pancreatic cancer cells by targeting p120 catenin.J Cell Physiol 2013;228:1255-1263[PMID:23139153 DOI:10 .1002/jcp.24280]
74 Chang CJ,Chao CH,Xia W,Yang JY,Xiong Y,Li CW,Yu WH,Rehman SK,Hsu JL,Lee HH,Liu M,Chen CT,Yu D,Hung MC.p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating mi RNAs.Nat Cell Biol 2011;13:317-323[PMID:21336307 DOI:10.1038/ncb2173]
75 Chen D,Zhang Y,Wang J,Chen J,Yang C,Cai K,Wang X,Shi F,Dou J.Micro RNA-200c overexpression inhibits tumorigenicity and metastasis of CD117+CD44+ovarian cancer stem cells by regulating epithelial-mesenchymal transition.J Ovarian Res 2013;6:50[PMID:23842108 DOI:10.1186/1757-2215-6-50]
76 Han M,Liu M,Wang Y,Chen X,Xu J,Sun Y,Zhao L,Qu H,Fan Y,Wu C.Antagonism of mi R-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2inactivation by targeting PTEN.PLo S One 2012;7:e39520[PMID:22761812 DOI:10.1371/journal.pone.0039520]
77 Tsai JH,Donaher JL,Murphy DA,Chau S,Yang J.Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis.Cancer Cell 2012;22:725-736[PMID:23201165 DOI:10.1016/j.ccr.2012.09.022]
78 Siemens H,Jackstadt R,Hünten S,Kaller M,Menssen A,G?tz U,Hermeking H.mi R-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions.Cell Cycle 2011;10:4256-4271[PMID:22134354 DOI:10.4161/cc.10.24.18552]
79 Brabletz S,Brabletz T.The ZEB/mi R-200 feedback loop--a motor of cellular plasticity in development and cancer?EMBO Rep 2010;11:670-677[PMID:20706219 DOI:10.1038/embor.2010.117]
80 Moes M,Le Béchec A,Crespo I,Laurini C,Halavatyi A,Vetter G,Del Sol A,Friederich E.A novel network integrating a mi RNA-203/SNAI1 feedback loop which regulates epithelial to mesenchymal transition.PLo S One 2012;7:e35440[PMID:22514743 DOI:10.1371/journal.pone.0035440]
81 Fuchs E,Tumbar T,Guasch G.Socializing with the neighbors:stem cells and their niche.Cell 2004;116:769-778[PMID:15035980]
82 Li L,Neaves WB.Normal stem cells and cancer stem cells:the niche matters.Cancer Res 2006;66:4553-4557[PMID:16651403]
83 Kuhn NZ,Tuan RS.Regulation of stemness and stem cell niche of mesenchymal stem cells:implications in tumorigenesis and metastasis.J Cell Physiol 2010;222:268-277[PMID:19847802DOI:10.1002/jcp.21940]
84 Borovski T,De Sousa E Melo F,Vermeulen L,Medema JP.Cancer stem cell niche:the place to be.Cancer Res 2011;71:634-639[PMID:21266356 DOI:10.1158/0008-5472.CAN-10-3220]
85 Cabarcas SM,Mathews LA,Farrar WL.The cancer stem cell niche--there goes the neighborhood?Int J Cancer 2011;129:2315-2327[PMID:21792897 DOI:10.1002/ijc.26312]
86 Méndez-Ferrer S,Michurina TV,Ferraro F,Mazloom AR,Macarthur BD,Lira SA,Scadden DT,Ma’ayan A,Enikolopov GN,Frenette PS.Mesenchymal and haematopoietic stem cells form a unique bone marrow niche.Nature 2010;466:829-834[PMID:20703299 DOI:10.1038/nature09262]
87 Winkler IG,Sims NA,Pettit AR,Barbier V,Nowlan B,Helwani F,Poulton IJ,van Rooijen N,Alexander KA,Raggatt LJ,Lévesque JP.Bone marrow macrophages maintain hematopoietic stem cell(HSC)niches and their depletion mobilizes HSCs.Blood 2010;116:4815-4828[PMID:20713966 DOI:10.1182/blood-2009-11-253534]
88 Li HJ,Reinhardt F,Herschman HR,Weinberg RA.Cancerstimulated mesenchymal stem cells create a carcinoma stem cell niche via prostaglandin E2 signaling.Cancer Discov 2012;2:840-855[PMID:22763855 DOI:10.1158/2159-8290.CD-12-0101]
89 Wang R,Chadalavada K,Wilshire J,Kowalik U,Hovinga KE,Geber A,Fligelman B,Leversha M,Brennan C,Tabar V.Glioblastoma stem-like cells give rise to tumour endothelium.Nature 2010;468:829-833[PMID:21102433 DOI:10.1038/nature09624]
90 Domanska UM,Kruizinga RC,Nagengast WB,Timmer-Bosscha H,Huls G,de Vries EG,Walenkamp AM.A review on CXCR4/CXCL12 axis in oncology:no place to hide.Eur J Cancer 2013;49:219-230[PMID:22683307 DOI:10.1016/j.ejca.2012.05.005]
91 Gherardi E,Birchmeier W,Birchmeier C,Vande Woude G.Targeting MET in cancer:rationale and progress.Nat Rev Cancer2012;12:89-103[PMID:22270953 DOI:10.1038/nrc3205]
92 Jamieson C,Sharma M,Henderson BR.Wnt signaling from membrane to nucleus:β-catenin caught in a loop.Int J Biochem Cell Biol 2012;44:847-850[PMID:22433990 DOI:10.1016/j.biocel.2012.03.001]
93 Ono M,Kosaka N,Tominaga N,Yoshioka Y,Takeshita F,Takahashi RU,Yoshida M,Tsuda H,Tamura K,Ochiya T.Exosomes from bone marrow mesenchymal stem cells contain a micro RNA that promotes dormancy in metastatic breast cancer cells.Sci Signal 2014;7:ra63[PMID:24985346 DOI:10.1126/scisignal.2005231]
94 Nakano I,Garnier D,Minata M,Rak J.Extracellular vesicles in the biology of brain tumour stem cells--Implications for intercellular communication,therapy and biomarker development.Semin Cell Dev Biol 2015;40:17-26[PMID:25721810 DOI:10 .1016/j.semcdb.2015.02.011]
95 Grange C,Tapparo M,Collino F,Vitillo L,Damasco C,Deregibus MC,Tetta C,Bussolati B,Camussi G.Microvesicles released from human renal cancer stem cells stimulate angiogenesis and formation of lung premetastatic niche.Cancer Res 2011;71:5346-5356[PMID:21670082 DOI:10.1158/0008-5472.CAN-11-0241]
96 Kaplan RN,Riba RD,Zacharoulis S,Bramley AH,Vincent L,Costa C,Mac Donald DD,Jin DK,Shido K,Kerns SA,Zhu Z,Hicklin D,Wu Y,Port JL,Altorki N,Port ER,Ruggero D,Shmelkov SV,Jensen KK,Rafii S,Lyden D.VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche.Nature 2005;438:820-827[PMID:16341007]
97 Alderton GK.Metastasis.Exosomes drive premetastatic niche formation.Nat Rev Cancer 2012;12:447[PMID:22722393 DOI:10 .1038/nrc3304]
98 Thuma F,Z?ller M.Outsmart tumor exosomes to steal the cancer initiating cell its niche.Semin Cancer Biol 2014;28:39-50[PMID:24631836 DOI:10.1016/j.semcancer.2014.02.011]
99 Suchorska WM,Lach MS.The role of exosomes in tumor progression and metastasis(Review).Oncol Rep 2016;35:1237-1244[PMID:26707854 DOI:10.3892/or.2015.4507]
100 Jung T,Castellana D,Klingbeil P,Cuesta Hernández I,Vitacolonna M,Orlicky DJ,Roffler SR,Brodt P,Z?ller M.CD44v6 dependence of premetastatic niche preparation by exosomes.Neoplasia 2009;11:1093-1105[PMID:19794968]
101 Costa-Silva B,Aiello NM,Ocean AJ,Singh S,Zhang H,Thakur BK,Becker A,Hoshino A,Mark MT,Molina H,Xiang J,Zhang T,Theilen TM,García-Santos G,Williams C,Ararso Y,Huang Y,Rodrigues G,Shen TL,Labori KJ,Lothe IM,Kure EH,Hernandez J,Doussot A,Ebbesen SH,Grandgenett PM,Hollingsworth MA,Jain M,Mallya K,Batra SK,Jarnagin WR,Schwartz RE,Matei I,Peinado H,Stanger BZ,Bromberg J,Lyden D.Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver.Nat Cell Biol 2015;17:816-826[PMID:25985394 DOI:10.1038/ncb3169]
102 Vlassov AV,Magdaleno S,Setterquist R,Conrad R.Exosomes:current knowledge of their composition,biological functions,and diagnostic and therapeutic potentials.Biochim Biophys Acta 2012;1820:940-948[PMID:22503788 DOI:10.1016/j.bbagen.2012.03.017]
103 Lo Cicero A,Stahl PD,Raposo G.Extracellular vesicles shuffling intercellular messages:for good or for bad.Curr Opin Cell Biol2015;35:69-77[PMID:26001269 DOI:10.1016/j.ceb.2015.04.013]
104 Henne WM,Buchkovich NJ,Emr SD.The ESCRT pathway.Dev Cell 2011;21:77-91[PMID:21763610 DOI:10.1016/j.devcel.2011.05.015]
105 Colombo M,Moita C,van Niel G,Kowal J,Vigneron J,Benaroch P,Manel N,Moita LF,Théry C,Raposo G.Analysis of ESCRT functions in exosome biogenesis,composition and secretion highlights the heterogeneity of extracellular vesicles.J Cell Sci 2013;126:5553-5565[PMID:24105262 DOI:10.1242/jcs.128868]
106 Baietti MF,Zhang Z,Mortier E,Melchior A,Degeest G,Geeraerts A,Ivarsson Y,Depoortere F,Coomans C,Vermeiren E,Zimmermann P,David G.Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.Nat Cell Biol 2012;14:677-685[PMID:22660413 DOI:10.1038/ncb2502]
107 Z?ller M.Tetraspanins:push and pull in suppressing and promoting metastasis.Nat Rev Cancer 2009;9:40-55[PMID:19078974 DOI:10.1038/nrc2543]
108 van Niel G,Charrin S,Simoes S,Romao M,Rochin L,Saftig P,Marks MS,Rubinstein E,Raposo G.The tetraspanin CD63regulates ESCRT-independent and-dependent endosomal sorting during melanogenesis.Dev Cell 2011;21:708-721[PMID:21962903 DOI:10.1016/j.devcel.2011.08.019]
109 Chairoungdua A,Smith DL,Pochard P,Hull M,Caplan MJ.Exosome release ofβ-catenin:a novel mechanism that antagonizes Wnt signaling.J Cell Biol 2010;190:1079-1091[PMID:20837771 DOI:10.1083/jcb.201002049]
110 Kajimoto T,Okada T,Miya S,Zhang L,Nakamura S.Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes.Nat Commun2013;4:2712[PMID:24231649 DOI:10.1038/ncomms3712]
111 Kelly EE,Horgan CP,Goud B,Mc Caffrey MW.The Rab family of proteins:25 years on.Biochem Soc Trans 2012;40:1337-1347[PMID:23176478 DOI:10.1042/BST20120203]
112 Record M,Carayon K,Poirot M,Silvente-Poirot S.Exosomes a s n e w v e s i c u l a r l i p i d t r a n s p o r t e r s i n v o l v e d i n c e l l-c e l l communication and various pathophysiologies.Biochim Biophys Acta 2014;1841:108-120[PMID:24140720 DOI:10.1016/j.bbalip.2013.10.004]
113 Subra C,Grand D,Laulagnier K,Stella A,Lambeau G,Paillasse M,De Medina P,Monsarrat B,Perret B,Silvente-Poirot S,Poirot M,Record M.Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins.J Lipid Res 2010;51:2105-2120[PMID:20424270 DOI:10.1194/jlr.M003657]
114 Katzmann DJ,Odorizzi G,Emr SD.Receptor downregulation and multivesicular-body sorting.Nat Rev Mol Cell Biol 2002;3:893-905[PMID:12461556]
115 Costanzo M,Baryshnikova A,Bellay J,Kim Y,Spear ED,Sevier CS,Ding H,Koh JL,Toufighi K,Mostafavi S,Prinz J,St Onge RP,Vander Sluis B,Makhnevych T,Vizeacoumar FJ,Alizadeh S,Bahr S,Brost RL,Chen Y,Cokol M,Deshpande R,Li Z,Lin ZY,Liang W,Marback M,Paw J,San Luis BJ,Shuteriqi E,Tong AH,van Dyk N,Wallace IM,Whitney JA,Weirauch MT,Zhong G,Zhu H,Houry WA,Brudno M,Ragibizadeh S,Papp B,Pál C,Roth FP,Giaever G,Nislow C,Troyanskaya OG,Bussey H,Bader GD,Gingras AC,Morris QD,Kim PM,Kaiser CA,Myers CL,Andrews BJ,Boone C.The genetic landscape of a cell.Science 2010;327:425-431[PMID:20093466 DOI:10.1126/science.1180823]
116 Ramstedt B,Slotte JP.Membrane properties of sphingomyelins.FEBS Lett 2002;531:33-37[PMID:12401199]
117 Allen TM,Austin GA,Chonn A,Lin L,Lee KC.Uptake of liposomes by cultured mouse bone marrow macrophages:influence of liposome composition and size.Biochim Biophys Acta 1991;1061:56-64[PMID:1995057]
118 Chernomordik LV,Kozlov MM.Protein-lipid interplay in fusion and fission of biological membranes.Annu Rev Biochem 2003;72:175-207[PMID:14527322]
119 Subra C,Laulagnier K,Perret B,Record M.Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies.Biochimie 2007;89:205-212[PMID:17157973]
120 Trajkovic K,Hsu C,Chiantia S,Rajendran L,Wenzel D,Wieland F,Schwille P,Brügger B,Simons M.Ceramide triggers budding of exosome vesicles into multivesicular endosomes.Science 2008;319:1244-1247[PMID:18309083 DOI:10.1126/science.1153124]
121 Schey KL,Luther JM,Rose KL.Proteomics characterization of exosome cargo.Methods 2015;87:75-82[PMID:25837312 DOI:10 .1016/j.ymeth.2015.03.018]
122 Mathivanan S,Ji H,Simpson RJ.Exosomes:extracellular organelles important in intercellular communication.J Proteomics2 0 1 0;7 3:1907-1920[PMID:20601276 DOI:10.1016/j.jprot.2010.06.006]
123 Shen B,Fang Y,Wu N,Gould SJ.Biogenesis of the posterior pole is mediated by the exosome/microvesicle protein-sorting pathway.J Biol Chem 2011;286:44162-44176[PMID:21865156 DOI:10 .1074/jbc.M111.274803]
124 Rana S,Claas C,Kretz CC,Nazarenko I,Zoeller M.Activationinduced internalization differs for the tetraspanins CD9 and Tspan8:Impact on tumor cell motility.Int J Biochem Cell Biol 2011;43:106-119[PMID:20937409 DOI:10.1016/j.biocel.2010.10.002]
125 Guo BB,Bellingham SA,Hill AF.The neutral sphingomyelinase pathway regulates packaging of the prion protein into exosomes.J Biol Chem 2015;290:3455-3467[PMID:25505180 DOI:10 .1074/jbc.M114.605253]
126 Nabhan JF,Hu R,Oh RS,Cohen SN,Lu Q.Formation and release of arrestin domain-containing protein 1-mediated microvesicles(ARMMs)at plasma membrane by recruitment of TSG101 protein.Proc Natl Acad Sci USA 2012;109:4146-4151[PMID:22315426 DOI:10.1073/pnas.1200448109]
127 Shen B,Wu N,Yang JM,Gould SJ.Protein targeting to exosomes/microvesicles by plasma membrane anchors.J Biol Chem2011;286:14383-14395[PMID:21300796 DOI:10.1074/jbc.M110.208660]
128 Hoshino D,Kirkbride KC,Costello K,Clark ES,Sinha S,GregaLarson N,Tyska MJ,Weaver AM.Exosome secretion is enhanced by invadopodia and drives invasive behavior.Cell Rep 2013;5:1159-1168[PMID:24290760 DOI:10.1016/j.celrep.2013.10.050]
129 Rana S,Yue S,Stadel D,Z?ller M.Toward tailored exosomes:the exosomal tetraspanin web contributes to target cell selection.Int J Biochem Cell Biol 2012;44:1574-1584[PMID:22728313 DOI:10 .1016/j.biocel.2012.06.018]
130 Yue S,Mu W,Erb U,Z?ller M.The tetraspanins CD151 and Tspan8 are essential exosome components for the crosstalk between cancer initiating cells and their surrounding.Oncotarget2015;6:2366-2384[PMID:25544774]
131 Choi DS,Yang JS,Choi EJ,Jang SC,Park S,Kim OY,Hwang D,Kim KP,Kim YK,Kim S,Gho YS.The protein interaction network of extracellular vesicles derived from human colorectal cancer cells.J Proteome Res 2012;11:1144-1151[PMID:22149170 DOI:10 .1021/pr200842h]
132 Ji H,Greening DW,Barnes TW,Lim JW,Tauro BJ,Rai A,Xu R,Adda C,Mathivanan S,Zhao W,Xue Y,Xu T,Zhu HJ,Simpson RJ.Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components.Proteomics 2013;13:1672-1686[PMID:23585443 DOI:10.1002/pmic.201200562]
133 Al-Nedawi K,Meehan B,Micallef J,Lhotak V,May L,Guha A,Rak J.Intercellular transfer of the oncogenic receptor EGFRv III by microvesicles derived from tumour cells.Nat Cell Biol 2008;10:619-624[PMID:18425114 DOI:10.1038/ncb1725]
134 Corcoran C,Rani S,O’Brien K,O’Neill A,Prencipe M,Sheikh R,Webb G,Mc Dermott R,Watson W,Crown J,O’Driscoll L.Docetaxel-resistance in prostate cancer:evaluating associated phenotypic changes and potential for resistance transfer via exosomes.PLo S One 2012;7:e50999[PMID:23251413 DOI:10 .1371/journal.pone.0050999]
135 Park JA,Sharif AS,Tschumperlin DJ,Lau L,Limbrey R,Howarth P,Drazen JM.Tissue factor-bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo.J Allergy Clin Immunol 2012;130:1375-1383[PMID:22828416 DOI:10.1016/j.jaci.2012.05.031]
136 Demory Beckler M,Higginbotham JN,Franklin JL,Ham AJ,Halvey PJ,Imasuen IE,Whitwell C,Li M,Liebler DC,Coffey RJ.Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS.Mol Cell Proteomics 2013;12:343-355[PMID:23161513 DOI:10.1074/mcp.M112.022806]
137 Kumar D,Gupta D,Shankar S,Srivastava RK.Biomolecular characterization of exosomes released from cancer stem cells:Possible implications for biomarker and treatment of cancer.Oncotarget 2015;6:3280-3291[PMID:25682864]
138 Z?ller M.Exosomes in Cancer Disease.Methods Mol Biol 2016;1381:111-149[PMID:26667458 DOI:10.1007/978-1-4939-3204-7 _7]
139 Gibbings DJ,Ciaudo C,Erhardt M,Voinnet O.Multivesicular bodies associate with components of mi RNA effector complexes and modulate mi RNA activity.Nat Cell Biol 2009;11:1143-1149[PMID:19684575 DOI:10.1038/ncb1929]
140 Balaj L,Lessard R,Dai L,Cho YJ,Pomeroy SL,Breakefield XO,Skog J.Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences.Nat Commun 2011;2:180[PMID:21285958 DOI:10.1038/ncomms1180]
141 Salido-Guadarrama I,Romero-Cordoba S,Peralta-Zaragoza O,Hidalgo-Miranda A,Rodríguez-Dorantes M.Micro RNAs transported by exosomes in body fluids as mediators of intercellular communication in cancer.Onco Targets Ther 2014;7:1327-1338[PMID:25092989 DOI:10.2147/OTT.S61562]
142 Valadi H,Ekstr?m K,Bossios A,Sj?strand M,Lee JJ,L?tvall JO.Exosome-mediated transfer of m RNAs and micro RNAs is a novel mechanism of genetic exchange between cells.Nat Cell Biol 2007;9:654-659[PMID:17486113]
143 Turchinovich A,Weiz L,Langheinz A,Burwinkel B.Characterization of extracellular circulating micro RNA.Nucleic Acids Res 2011;39:7223-7233[PMID:21609964 DOI:10.1093/nar/gkr254]
144 Vedeler A,Holl?s H,Grindheim AK,Raddum AM.Multiple roles of annexin A2 in post-transcriptional regulation of gene expression.Curr Protein Pept Sci 2012;13:401-412[PMID:22708494]
145 Villarroya-Beltri C,Gutiérrez-Vázquez C,Sánchez-Cabo F,Pérez-Hernández D,Vázquez J,Martin-Cofreces N,MartinezHerrera DJ,Pascual-Montano A,Mittelbrunn M,Sánchez-Madrid F.Sumoylated hn RNPA2B1 controls the sorting of mi RNAs into exosomes through binding to specific motifs.Nat Commun 2013;4:2980[PMID:24356509 DOI:10.1038/ncomms3980]
146 Kogure T,Yan IK,Lin WL,Patel T.Extracellular VesicleMediated Transfer of a Novel Long Noncoding RNA TUC339:A Mechanism of Intercellular Signaling in Human Hepatocellular Cancer.Genes Cancer 2013;4:261-272[PMID:24167654 DOI:10 .1177/1947601913499020]
147 Pinto R,De Summa S,Petriella D,Tudoran O,Danza K,Tommasi S.The value of new high-throughput technologies for diagnosis and prognosis in solid tumors.Cancer Biomark 2014;14:103-117[PMID:24878811 DOI:10.3233/CBM-130328]
148 Iwakawa HO,Tomari Y.The Functions of Micro RNAs:m RNA Decay and Translational Repression.Trends Cell Biol 2015;25:651-665[PMID:26437588 DOI:10.1016/j.tcb.2015.07.011]
149 Sato-Kuwabara Y,Melo SA,Soares FA,Calin GA.The fusion of two worlds:non-coding RNAs and extracellular vesicles--diagnostic and therapeutic implications(Review).Int J Oncol2015;46:17-27[PMID:25338714 DOI:10.3892/ijo.2014.2712]
150 Garg M.Targeting micro RNAs in epithelial-to-mesenchymal transition-induced cancer stem cells:therapeutic approaches in cancer.Expert Opin Ther Targets 2015;19:285-297[PMID:25563894 DOI:10.1517/14728222.2014.975794]
151 Garofalo M,Croce CM.Role of micro RNAs in maintaining cancer stem cells.Adv Drug Deliv Rev 2015;81:53-61[PMID:25446141 DOI:10.1016/j.addr.2014.11.014]
152 Katoh M.Therapeutics targeting angiogenesis:genetics and epigenetics,extracellular mi RNAs and signaling networks(Review).Int J Mol Med 2013;32:763-767[PMID:23863927DOI:10.3892/ijmm.2013.1444]
153 Palma J,Yaddanapudi SC,Pigati L,Havens MA,Jeong S,Weiner GA,Weimer KM,Stern B,Hastings ML,Duelli DM.Micro RNAs are exported from malignant cells in customized particles.Nucleic Acids Res 2012;40:9125-9138[PMID:22772984 DOI:10.1093/nar/gks656]
154 Rappa G,Mercapide J,Anzanello F,Pope RM,Lorico A.Biochemical and biological characterization of exosomes containing prominin-1/CD133.Mol Cancer 2013;12:62[PMID:23767874 DOI:10.1186/1476-4598-12-62]
155 Silva A,Bullock M,Calin G.The Clinical Relevance of Long Non-Coding RNAs in Cancer.Cancers(Basel)2015;7:2169-2182[PMID:26516918 DOI:10.3390/cancers7040884]
156 Fitzgerald TL,Mc Cubrey JA.Pancreatic cancer stem cells:association with cell surface markers,prognosis,resistance,metastasis and treatment.Adv Biol Regul 2014;56:45-50[PMID:24925031 DOI:10.1016/j.jbior.2014.05.001]
157 Abel EV,Simeone DM.Biology and clinical applications of pancreatic cancer stem cells.Gastroenterology 2013;144:1241-1248[PMID:23622133 DOI:10.1053/j.gastro.2013.01.072]
158 Ohara Y,Oda T,Sugano M,Hashimoto S,Enomoto T,Yamada K,Akashi Y,Miyamoto R,Kobayashi A,Fukunaga K,Morishita Y,Ohkohchi N.Histological and prognostic importance of CD44(+)/CD24(+)/Ep CAM(+)expression in clinical pancreatic cancer.Cancer Sci 2013;104:1127-1134[PMID:23679813 DOI:10.1111/cas.12198]
159 Hori Y.Prominin-1(CD133)Reveals New Faces of Pancreatic Progenitor Cells and Cancer Stem Cells:Current Knowledge and Therapeutic Perspectives.Adv Exp Med Biol 2013;777:185-196[PMID:23161083 DOI:10.1007/978-1-4614-5894-4_12]
160 Balic A,Dorado J,Alonso-Gómez M,Heeschen C.Stem cells as the root of pancreatic ductal adenocarcinoma.Exp Cell Res 2012;318:691-704[PMID:22119145 DOI:10.1016/j.yexcr.2011.11.007]
161 Vaz AP,Ponnusamy MP,Seshacharyulu P,Batra SK.A concise review on the current understanding of pancreatic cancer stem cells.J Cancer Stem Cell Res 2014;2:e1004[PMID:26451384]
162 Wang H,Rana S,Giese N,Büchler MW,Z?ller M.Tspan8,CD44v6 and alpha6beta4 are biomarkers of migrating pancreatic cancer-initiating cells.Int J Cancer 2013;133:416-426[PMID:23338841 DOI:10.1002/ijc.28044]
163 Li C,Wu JJ,Hynes M,Dosch J,Sarkar B,Welling TH,Pasca di Magliano M,Simeone DM.c-Met is a marker of pancreatic cancer stem cells and therapeutic target.Gastroenterology2011;141:2218-2227.e5[PMID:21864475 DOI:10.1053/j.gastro.2011.08.009]
164 Saito S,Okabe H,Watanabe M,Ishimoto T,Iwatsuki M,Baba Y,Tanaka Y,Kurashige J,Miyamoto Y,Baba H.CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer.Oncol Rep 2013;29:1570-1578[PMID:23404221 DOI:10.3892/or.2013.2273]
165 Todaro M,Gaggianesi M,Catalano V,Benfante A,Iovino F,Biffoni M,Apuzzo T,Sperduti I,Volpe S,Cocorullo G,Gulotta G,Dieli F,De Maria R,Stassi G.CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis.Cell Stem Cell 2014;14:342-356[PMID:24607406DOI:10.1016/j.stem.2014.01.009]
166 Dalla Pozza E,Dando I,Biondani G,Brandi J,Costanzo C,Zoratti E,Fassan M,Boschi F,Melisi D,Cecconi D,Scupoli MT,Scarpa A,Palmieri M.Pancreatic ductal adenocarcinoma cell lines display a plastic ability to bi-directionally convert into cancer stem cells.Int J Oncol 2015;46:1099-1108[PMID:25502497 DOI:10.3892/ijo.2014.2796]
167 Klingbeil P,Marhaba R,Jung T,Kirmse R,Ludwig T,Z?ller M.CD44 variant isoforms promote metastasis formation by a tumor cell-matrix cross-talk that supports adhesion and apoptosis resistance.Mol Cancer Res 2009;7:168-179[PMID:19208744DOI:10.1158/1541-7786.MCR-08-0207]
168 Matzke-Ogi A,Jannasch K,Shatirishvili M,Fuchs B,Chiblak S,Morton J,Tawk B,Lindner T,Sansom O,Alves F,Warth A,Schwager C,Mier W,Kleeff J,Ponta H,Abdollahi A,OrianRousseau V.Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling.Gastroenterology 2016;150:513-25.e10[PMID:26597578 DOI:10 .1053/j.gastro.2015.10.020]
169 Chen K,Li Z,Jiang P,Zhang X,Zhang Y,Jiang Y,He Y,Li X.Co-expression of CD133,CD44v6 and human tissue factor is associated with metastasis and poor prognosis in pancreatic carcinoma.Oncol Rep 2014;32:755-763[PMID:24920554 DOI:10 .3892/or.2014.3245]
170 Aruffo A,Stamenkovic I,Melnick M,Underhill CB,Seed B.CD44 is the principal cell surface receptor for hyaluronate.Cell1990;61:1303-1313[PMID:1694723]
171 Ishii S,Ford R,Thomas P,Nachman A,Steele G,Jessup JM.CD44 participates in the adhesion of human colorectal carcinoma cells to laminin and type IV collagen.Surg Oncol 1993;2:255-264[PMID:7504563]
172 Jalkanen S,Jalkanen M.Lymphocyte CD44 binds the COOHterminal heparin-binding domain of fibronectin.J Cell Biol 1992;116:817-825[PMID:1730778]
173 Konstantopoulos K,Thomas SN.Cancer cells in transit:the vascular interactions of tumor cells.Annu Rev Biomed Eng2009;11:177-202[PMID:19413512 DOI:10.1146/annurevbioeng-061008-124949]
174 Kim MS,Park MJ,Moon EJ,Kim SJ,Lee CH,Yoo H,Shin SH,Song ES,Lee SH.Hyaluronic acid induces osteopontin via the phosphatidylinositol 3-kinase/Akt pathway to enhance the motility of human glioma cells.Cancer Res 2005;65:686-691[PMID:15705860]
175 Khan SA,Cook AC,Kappil M,Günthert U,Chambers AF,Tuck AB,Denhardt DT.Enhanced cell surface CD44 variant(v6,v9)expression by osteopontin in breast cancer epithelial cells facilitates tumor cell migration:novel post-transcriptional,posttranslational regulation.Clin Exp Metastasis 2005;22:663-673[PMID:16691370]
176 Tremmel M,Matzke A,Albrecht I,Laib AM,Olaku V,BallmerHofer K,Christofori G,Héroult M,Augustin HG,Ponta H,Orian-Rousseau V.A CD44v6 peptide reveals a role of CD44 in VEGFR-2 signaling and angiogenesis.Blood 2009;114:5236-5244[PMID:19773544 DOI:10.1182/blood-2009-04-219204]
177 Z?ller M.CD44:can a cancer-initiating cell profit from an abundantly expressed molecule?Nat Rev Cancer 2011;11:254-267[PMID:21390059 DOI:10.1038/nrc3023]
178 Kollet O,Dar A,Shivtiel S,Kalinkovich A,Lapid K,Sztainberg Y,Tesio M,Samstein RM,Goichberg P,Spiegel A,Elson A,Lapidot T.Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells.Nat Med 2006;12:657-664[PMID:16715089]
179 Weber GF,Bronson RT,Ilagan J,Cantor H,Schmits R,Mak TW.Absence of the CD44 gene prevents sarcoma metastasis.Cancer Res 2002;62:2281-2286[PMID:11956084]
180 Williams K,Motiani K,Giridhar PV,Kasper S.CD44 integrates signaling in normal stem cell,cancer stem cell and(pre)metastatic niches.Exp Biol Med(Maywood)2013;238:324-338[PMID:23598979 DOI:10.1177/1535370213480714]
181 Trusolino L,Bertotti A,Comoglio PM.MET signalling:principles and functions in development,organ regeneration and cancer.Nat Rev Mol Cell Biol 2010;11:834-848[PMID:21102609 DOI:10 .1038/nrm3012]
182 Lokeshwar VB,Fregien N,Bourguignon LY.Ankyrin-binding domain of CD44(GP85)is required for the expression of hyaluronic acid-mediated adhesion function.J Cell Biol 1994;126:1099-1109[PMID:7519619]
183 Fehon RG,Mc Clatchey AI,Bretscher A.Organizing the cell cortex:the role of ERM proteins.Nat Rev Mol Cell Biol 2010;11:276-287[PMID:20308985 DOI:10.1038/nrm2866]
184 Mori T,Kitano K,Terawaki S,Maesaki R,Fukami Y,Hakoshima T.Structural basis for CD44 recognition by ERM proteins.J Biol Chem 2008;283:29602-29612[PMID:18753140 DOI:10.1074/jbc.M803606200]
185 Nagano O,Saya H.Mechanism and biological significance of CD44 cleavage.Cancer Sci 2004;95:930-935[PMID:15596040]
186 Okamoto I,Kawano Y,Murakami D,Sasayama T,Araki N,Miki T,Wong AJ,Saya H.Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway.J Cell Biol 2001;155:755-762[PMID:11714729]
187 Miletti-González KE,Murphy K,Kumaran MN,Ravindranath AK,Wernyj RP,Kaur S,Miles GD,Lim E,Chan R,Chekmareva M,Heller DS,Foran D,Chen W,Reiss M,Bandera EV,Scotto K,Rodríguez-Rodríguez L.Identification of function for CD44intracytoplasmic domain(CD44-ICD):modulation of matrix metalloproteinase 9(MMP-9)transcription via novel promoter response element.J Biol Chem 2012;287:18995-19007[PMID:22433859 DOI:10.1074/jbc.M111.318774]
188 Pietras A,Katz AM,Ekstr?m EJ,Wee B,Halliday JJ,Pitter KL,Werbeck JL,Amankulor NM,Huse JT,Holland EC.OsteopontinCD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth.Cell Stem Cell 2014;14:357-369[PMID:24607407 DOI:10.1016/j.stem.2014.01.005]
189 Oliferenko S,Paiha K,Harder T,Gerke V,Schw?rzler C,Schwarz H,Beug H,Günthert U,Huber LA.Analysis of CD44-containing lipid rafts:Recruitment of annexin II and stabilization by the actin cytoskeleton.J Cell Biol 1999;146:843-854[PMID:10459018]
190 Zarbock A,Ley K,Mc Ever RP,Hidalgo A.Leukocyte ligands for endothelial selectins:specialized glycoconjugates that mediate rolling and signaling under flow.Blood 2011;118:6743-6751[PMID:22021370 DOI:10.1182/blood-2011-07-343566]
191 F?ger N,Marhaba R,Z?ller M.Involvement of CD44 in cytoskeleton rearrangement and raft reorganization in T cells.J Cell Sci 2001;114:1169-1178[PMID:11228160]
192 Róg T,Vattulainen I.Cholesterol,sphingolipids,and glycolipids:what do we know about their role in raft-like membranes?Chem Phys Lipids 2014;184:82-104[PMID:25444976 DOI:10.1016/j.chemphyslip.2014.10.004]
193 Lin ML,Lu YC,Chen HY,Lee CC,Chung JG,Chen SS.Suppressing the formation of lipid raft-associated Rac1/PI3K/Akt signaling complexes by curcumin inhibits SDF-1α-induced invasion of human esophageal carcinoma cells.Mol Carcinog2014;53:360-379[PMID:23192861 DOI:10.1002/mc.21984]
194 Ratajczak MZ,Lee H,Wysoczynski M,Wan W,Marlicz W,Laughlin MJ,Kucia M,Janowska-Wieczorek A,Ratajczak J.Novel insight into stem cell mobilization-plasma sphingosine-1 -phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex.Leukemia 2010;24:976-985[PMID:20357827 DOI:10.1038/leu.2010.53]
195 Desai B,Ma T,Zhu J,Chellaiah MA.Characterization of the expression of variant and standard CD44 in prostate cancer cells:identification of the possible molecular mechanism of CD44/MMP9 complex formation on the cell surface.J Cell Biochem2009;108:272-284[PMID:19582779 DOI:10.1002/jcb.22248]
196 Bourguignon LY,Gunja-Smith Z,Iida N,Zhu HB,Young LJ,Muller WJ,Cardiff RD.CD44v(3,8-10)is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase(MMP-9)association in metastatic breast cancer cells.J Cell Physiol 1998;176:206-215[PMID:9618160]
197 Zarzynska JM.Two faces of TGF-beta1 in breast cancer.Mediators Inflamm 2014;2014:141747[PMID:24891760 DOI:10 .1155/2014/141747]
198 Takahashi E,Nagano O,Ishimoto T,Yae T,Suzuki Y,Shinoda T,Nakamura S,Niwa S,Ikeda S,Koga H,Tanihara H,Saya H.Tumor necrosis factor-alpha regulates transforming growth factorbeta-dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-moesin interaction.J Biol Chem 2010;285:4060-4073[PMID:19965872 DOI:10.1074/jbc.M109.056523]
199 Z?ller M.CD44,Hyaluronan,the Hematopoietic Stem Cell,and Leukemia-Initiating Cells.Front Immunol 2015;6:235[PMID:26074915 DOI:10.3389/fimmu.2015.00235]
200 Rutnam ZJ,Yang BB.The non-coding 3’UTR of CD44 induces metastasis by regulating extracellular matrix functions.J Cell Sci2012;125:2075-2085[PMID:22637644 DOI:10.1242/jcs100818]
201 Bourguignon LY,Earle C,Wong G,Spevak CC,Krueger K.Stem cell marker(Nanog)and Stat-3 signaling promote Micro RNA-21expression and chemoresistance in hyaluronan/CD44-activated head and neck squamous cell carcinoma cells.Oncogene 2012;31:149-160[PMID:21685938 DOI:10.1038/onc.2011.222]
202 Rana S,Malinowska K,Z?ller M.Exosomal tumor micro RNA modulates premetastatic organ cells.Neoplasia 2013;15:281-295[PMID:23479506 DOI:10.1593/neo.122010]
203 Delitto D,Vertes-George E,Hughes SJ,Behrns KE,Trevino JG.c-Met signaling in the development of tumorigenesis and chemoresistance:potential applications in pancreatic cancer.World J Gastroenterol 2014;20:8458-8470[PMID:25024602 DOI:10 .3748/wjg.v20.i26.8458]
204 Orian-Rousseau V,Morrison H,Matzke A,Kastilan T,Pace G,Herrlich P,Ponta H.Hepatocyte growth factor-induced Ras activation requires ERM proteins linked to both CD44v6 and F-actin.Mol Biol Cell 2007;18:76-83[PMID:17065554 DOI:10 .1091/mbc.E06-08-0674]
205 Maroun CR,Rowlands T.The Met receptor tyrosine kinase:a key player in oncogenesis and drug resistance.Pharmacol Ther 2014;142:316-338[PMID:24384534 DOI:10.1016/j.pharmthera.2013.12.014]
206 Marano L,Chiari R,Fabozzi A,De Vita F,Boccardi V,Roviello G,Petrioli R,Marrelli D,Roviello F,Patriti A.c-Met targeting in advanced gastric cancer:An open challenge.Cancer Lett 2015;365:30-36[PMID:26049023 DOI:10.1016/j.canlet.2015.05.028]
207 Jung T,Gross W,Z?ller M.CD44v6 coordinates tumor matrixtriggered motility and apoptosis resistance.J Biol Chem 2011;286:15862-15874[PMID:21372142 DOI:10.1074/jbc.M110.208421]
208 Ni J,Cozzi PJ,Hao JL,Beretov J,Chang L,Duan W,Shigdar S,Delprado WJ,Graham PH,Bucci J,Kearsley JH,Li Y.CD44variant 6 is associated with prostate cancer metastasis and chemo-/radioresistance.Prostate 2014;74:602-617[PMID:24615685DOI:10.1002/pros.22775]
209 Hasenauer S,Malinger D,Koschut D,Pace G,Matzke A,von Au A,Orian-Rousseau V.Internalization of Met requires the co-receptor CD44v6 and its link to ERM proteins.PLo S One 2013;8:e62357[PMID:23626807 DOI:10.1371/journal.pone.0062357]
210 Dallas NA,Xia L,Fan F,Gray MJ,Gaur P,van Buren G,Samuel S,Kim MP,Lim SJ,Ellis LM.Chemoresistant colorectal cancer cells,the cancer stem cell phenotype,and increased sensitivity to insulin-like growth factor-I receptor inhibition.Cancer Res2009;69:1951-1957[PMID:19244128 DOI:10.1158/0008-5472.CAN-08-2023]
211 Porsch H,Mehi?M,Olofsson B,Heldin P,Heldin CH.Plateletderived growth factorβ-receptor,transforming growth factorβtype I receptor,and CD44 protein modulate each other’s signaling and stability.J Biol Chem 2014;289:19747-19757[PMID:24860093 DOI:10.1074/jbc.M114.547273]
212 Sakai K,Aoki S,Matsumoto K.Hepatocyte growth factor and Met in drug discovery.J Biochem 2015;157:271-284[PMID:25770121 DOI:10.1093/jb/mvv027]
213 Maecker HT,Todd SC,Levy S.The tetraspanin superfamily:molecular facilitators.FASEB J 1997;11:428-442[PMID:9194523]
214 Hemler ME.Tetraspanin proteins promote multiple cancer stages.Nat Rev Cancer 2014;14:49-60[PMID:24505619]
215 Wang HX,Li Q,Sharma C,Knoblich K,Hemler ME.Tetraspanin protein contributions to cancer.Biochem Soc Trans 2011;39:547-552[PMID:21428937 DOI:10.1042/BST0390547]
216 Guo Q,Xia B,Zhang F,Richardson MM,Li M,Zhang JS,Chen F,Zhang XA.Tetraspanin CO-029 inhibits colorectal cancer cell movement by deregulating cell-matrix and cell-cell adhesions.PLo S One 2012;7:e38464[PMID:22679508 DOI:10.1371/journal.pone.0038464]
217 Berthier-Vergnes O,Kharbili ME,de la Fouchardière A,Pointecouteau T,Verrando P,Wierinckx A,Lachuer J,Le Naour F,Lamartine J.Gene expression profiles of human melanoma cells with different invasive potential reveal TSPAN8 as a novel mediator of invasion.Br J Cancer 2011;104:155-165[PMID:21081927 DOI:10.1038/sj.bjc.6605994]
218 Sterk LM,Geuijen CA,van den Berg JG,Claessen N,Weening JJ,Sonnenberg A.Association of the tetraspanin CD151 with the laminin-binding integrins alpha3beta1,alpha6beta1,alpha6beta4and alpha7beta1 in cells in culture and in vivo.J Cell Sci 2002;115:1161-1173[PMID:11884516]
219 Liu L,He B,Liu WM,Zhou D,Cox JV,Zhang XA.Tetraspanin CD151 promotes cell migration by regulating integrin trafficking.J Biol Chem 2007;282:31631-31642[PMID:17716972 DOI:10 .1074/jbc.M701165200]
220 Zijlstra A,Lewis J,Degryse B,Stuhlmann H,Quigley JP.The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151.Cancer Cell 2008;13:221-234[PMID:18328426 DOI:10.1016/j.ccr.2008.01.031]
221 Hong IK,Jeoung DI,Ha KS,Kim YM,Lee H.Tetraspanin CD151stimulates adhesion-dependent activation of Ras,Rac,and Cdc42by facilitating molecular association betweenβ1 integrins and small GTPases.J Biol Chem 2012;287:32027-32039[PMID:22843693 DOI:10.1074/jbc.M111.314443]
222 Yang XH,Mirchev R,Deng X,Yacono P,Yang HL,Golan DE,Hemler ME.CD151 restricts theα6 integrin diffusion mode.J Cell Sci 2012;125:1478-1487[PMID:22328509 DOI:10.1242/jcs.093963]
223 Wei L,Li Y,Suo Z.TSPAN8 promotes gastric cancer growth and metastasis via ERK MAPK pathway.Int J Clin Exp Med 2015;8:8599-8607[PMID:26309511]
224 Kim TK,Park CS,Jeoung MH,Lee WR,Go NK,Choi JR,Lee TS,Shim H,Lee S.Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells.Biochem Biophys Res Commun 2015;468:774-780[PMID:26562525 DOI:10.1016/j.bbrc.2015.11.031]
225 Zhu H,Wu Y,Zheng W,Lu S.CO-029 is overexpressed in gastric cancer and mediates the effects of EGF on gastric cancer cell proliferation and invasion.Int J Mol Med 2015;35:798-802[PMID:25592989 DOI:10.3892/ijmm.2015.2069]
226 Zhou Z,Ran YL,Hu H,Pan J,Li ZF,Chen LZ,Sun LC,Peng L,Zhao XL,Yu L,Sun LX,Yang ZH.TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression.Clin Exp Metastasis 2008;25:537-548[PMID:18365756 DOI:10 .1007/s10585-008-9168-0]
227 Hemler ME.Tetraspanin functions and associated microdomains.Nat Rev Mol Cell Biol 2005;6:801-811[PMID:16314869 DOI:10 .1038/nrm1736]
228 Levy S,Shoham T.Protein-protein interactions in the tetraspanin web.Physiology(Bethesda)2005;20:218-224[PMID:16024509DOI:10.1152/physiol.00015.2005]
229 Stipp CS,Kolesnikova TV,Hemler ME.Functional domains in tetraspanin proteins.Trends Biochem Sci 2003;28:106-112[PMID:12575999 DOI:10.1016/S0968-0004(02)00014-2]
230 Seigneuret M.Complete predicted three-dimensional structure of the facilitator transmembrane protein and hepatitis C virus receptor CD81:conserved and variable structural domains in the tetraspanin superfamily.Biophys J 2006;90:212-227[PMID:16352525 DOI:10 .1529/biophysj.105.069666]
231 Berditchevski F,Odintsova E,Sawada S,Gilbert E.Expression of the palmitoylation-deficient CD151 weakens the association of alpha 3 beta 1 integrin with the tetraspanin-enriched microdomains and affects integrin-dependent signaling.J Biol Chem 2002;277:36991-37000[PMID:12110679 DOI:10.1074/jbc.M205265200]
232 Delandre C,Penabaz TR,Passarelli AL,Chapes SK,Clem RJ.Mutation of juxtamembrane cysteines in the tetraspanin CD81affects palmitoylation and alters interaction with other proteins at the cell surface.Exp Cell Res 2009;315:1953-1963[PMID:19328198 DOI:10.1016/j.yexcr.2009.03.013]
233 Sharma C,Yang XH,Hemler ME.DHHC2 affects palmitoylation,stability,and functions of tetraspanins CD9 and CD151.Mol Biol Cell 2008;19:3415-3425[PMID:18508921 DOI:10.1091/mbc.E07-11-1164]
234 Todeschini AR,Dos Santos JN,Handa K,Hakomori SI.Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/c Met-mediated pathway.Proc Natl Acad Sci USA 2008;105:1925-1930[PMID:18272501 DOI:10.1073/pnas.0709619104]
235 Wang XQ,Yan Q,Sun P,Liu JW,Go L,Mc Daniel SM,Paller AS.Suppression of epidermal growth factor receptor signaling by protein kinase C-alpha activation requires CD82,caveolin-1,and ganglioside.Cancer Res 2007;67:9986-9995[PMID:17942932DOI:10.1158/0008-5472.CAN-07-1300]
236 Delaguillaumie A,Harriague J,Kohanna S,Bismuth G,Rubinstein E,Seigneuret M,Conjeaud H.Tetraspanin CD82 controls the association of cholesterol-dependent microdomains with the actin cytoskeleton in T lymphocytes:relevance to co-stimulation.J Cell Sci 2004;117:5269-5282[PMID:15454569 DOI:10.1242/jcs.01380]
237 Escola JM,Kleijmeer MJ,Stoorvogel W,Griffith JM,Yoshie O,Geuze HJ.Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.J Biol Chem 1998;273:20121-20127[PMID:9685355 DOI:10.1074/jbc.273.32.20121]
238 Berditchevski F,Odintsova E.Tetraspanins as regulators of protein trafficking.Traffic 2007;8:89-96[PMID:17181773 DOI:10 .1111/j.1600-0854.2006.00515.x]
239 Marks MS,Ohno H,Kirchnausen T,Bonracino JS.Protein sorting by tyrosine-based signals:adapting to the Ys and wherefores.Trends Cell Biol 1997;7:124-128[PMID:17708922 DOI:10 .1016/S0962-8924(96)10057-X]
240 Charrin S,le Naour F,Silvie O,Milhiet PE,Boucheix C,Rubinstein E.Lateral organization of membrane proteins:tetraspanins spin their web.Biochem J 2009;420:133-154[PMID:19426143 DOI:10.1042/BJ20082422]
241 Berditchevski F.Complexes of tetraspanins with integrins:more than meets the eye.J Cell Sci 2001;114:4143-4151[PMID:11739647]
242 Bassani S,Cingolani LA.Tetraspanins:Interactions and interplay with integrins.Int J Biochem Cell Biol 2012;44:703-708[PMID:22326999 DOI:10.1016/j.biocel.2012.01.020]
243 Herlevsen M,Schmidt DS,Miyazaki K,Z?ller M.The association of the tetraspanin D6.1A with the alpha6beta4 integrin supports cell motility and liver metastasis formation.J Cell Sci 2003;116:4373-4390[PMID:13130099 DOI:10.1242/jcs.00760]
244 Gesierich S,Paret C,Hildebrand D,Weitz J,Zgraggen K,SchmitzWinnenthal FH,Horejsi V,Yoshie O,Herlyn D,Ashman LK,Z?ller M.Colocalization of the tetraspanins,CO-029 and CD151,with integrins in human pancreatic adenocarcinoma:impact on cell motility.Clin Cancer Res 2005;11:2840-2852[PMID:15837731DOI:10.1158/1078-0432.CCR-04-1935]
245 Yue S,Mu W,Z?ller M.Tspan8 and CD151 promote metastasis by distinct mechanisms.Eur J Cancer 2013;49:2934-2948[PMID:23683890 DOI:10.1016/j.ejca.2013.03.032]
246 Gesierich S,Berezovskiy I,Ryschich E,Z?ller M.Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029.Cancer Res 2006;66:7083-7094[PMID:16849554 DOI:10 .1158/0008-5472.CAN-06-0391]
247 Nazarenko I,Rana S,Baumann A,Mc Alear J,Hellwig A,Trendelenburg M,Lochnit G,Preissner KT,Z?ller M.Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation.Cancer Res 2010;70:1668-1678[PMID:20124479 DOI:10.1158/0008-5472.CAN-09-2470]
248 Yá?ez-MóM,Gutiérrez-López MD,Caba?as C.Functional interplay between tetraspanins and proteases.Cell Mol Life Sci2011;68:3323-3335[PMID:21687991 DOI:10.1007/s00018-011 -0746-y]
249 Le Naour F,AndréM,Greco C,Billard M,Sordat B,Emile JF,Lanza F,Boucheix C,Rubinstein E.Profiling of the tetraspanin web of human colon cancer cells.Mol Cell Proteomics 2006;5:845-857[PMID:16467180 DOI:10.1074/mcp.M500330-MCP200]
250 Wang GP,Han XF.CD9 modulates proliferation of human glioblastoma cells via epidermal growth factor receptor signaling.Mol Med Rep 2015;12:1381-1386[PMID:25760022 DOI:10 .3892/mmr.2015.3466]
251 Sridhar SC,Miranti CK.Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases.Oncogene 2006;25:2367-2378[PMID:16331263 DOI:10.1038/sj.onc.1209269]
252 Little KD,Hemler ME,Stipp CS.Dynamic regulation of a GPCRtetraspanin-G protein complex on intact cells:central role of CD81 in facilitating GPR56-Galpha q/11 association.Mol Biol Cell 2004;15:2375-2387[PMID:15004227 DOI:10.1091/mbc.E03-12-0886]
253 Feng S,Agoulnik IU,Truong A,Li Z,Creighton CJ,Kaftanovskaya EM,Pereira R,Han HD,Lopez-Berestein G,Klonisch T,Ittmann MM,Sood AK,Agoulnik AI.Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis.Endocr Relat Cancer 2010;17:1021-1033[PMID:20861284 DOI:10.1677/ERC-10-0073]
254 AndréM,Le Caer JP,Greco C,Planchon S,El Nemer W,Boucheix C,Rubinstein E,Chamot-Rooke J,Le Naour F.Proteomic analysis of the tetraspanin web using LC-ESI-MS/MS and MALDI-FTICR-MS.Proteomics 2006;6:1437-1449[PMID:16404722 DOI:10.1002/pmic.200500180]
255 Zhang XA,Bontrager AL,Hemler ME.Transmembrane-4superfamily proteins associate with activated protein kinase C(PKC)and link PKC to specific beta(1)integrins.J Biol Chem2001;276:25005-25013[PMID:11325968 DOI:10.1074/jbc.M102156200]
256 Claas C,Stipp CS,Hemler ME.Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts.J Biol Chem 2001;276:7974-7984[PMID:11113129DOI:10.1074/jbc.M008650200]
257 Claas C,Wahl J,Orlicky DJ,Karaduman H,Schn?lzer M,Kempf T,Z?ller M.The tetraspanin D6.1A and its molecular partners on rat carcinoma cells.Biochem J 2005;389:99-110[PMID:15725074DOI:10.1042/BJ20041287]
258 Le Naour F,AndréM,Boucheix C,Rubinstein E.Membrane microdomains and proteomics:lessons from tetraspanin microdomains and comparison with lipid rafts.Proteomics 2006;6:6447-6454[PMID:17109380 DOI:10.1002/pmic.200600282]
259 Kuhn S,Koch M,Nübel T,Ladwein M,Antolovic D,Klingbeil P,Hildebrand D,Moldenhauer G,Langbein L,Franke WW,Weitz J,Z?ller M.A complex of Ep CAM,claudin-7,CD44 variant isoforms,and tetraspanins promotes colorectal cancer progression.Mol Cancer Res 2007;5:553-567[PMID:17579117 DOI:10 .1158/1541-7786.MCR-06-0384]
260 Yá?ez-MóM,Barreiro O,Gordon-Alonso M,Sala-Valdés M,Sánchez-Madrid F.Tetraspanin-enriched microdomains:a functional unit in cell plasma membranes.Trends Cell Biol 2009;19:434-446[PMID:19709882 DOI:10.1016/j.tcb.2009.06.004]
261 Hemler ME.Tetraspanin proteins mediate cellular penetration,invasion,and fusion events and define a novel type of membrane microdomain.Annu Rev Cell Dev Biol 2003;19:397-422[PMID:14570575 DOI:10.1146/annurev.cellbio.19.111301.153609]
262 Andreu Z,Yá?ez-MóM.Tetraspanins in extracellular vesicle formation and function.Front Immunol 2014;5:442[PMID:25278937 DOI:10.3389/fimmu.2014.00442]
263 Scheffer KD,Gawlitza A,Spoden GA,Zhang XA,Lambert C,Berditchevski F,Florin L.Tetraspanin CD151 mediates papillomavirus type 16 endocytosis.J Virol 2013;87:3435-3446[PMID:23302890 DOI:10.1128/JVI.02906-12]
264 Stipp CS.Laminin-binding integrins and their tetraspanin partners as potential antimetastatic targets.Expert Rev Mol Med 2010;12:e3[PMID:20078909 DOI:10.1017/S1462399409001355]
265 Klinovska K,Sebkova N,Dvorakova-Hortova K.Sperm-egg fusion:a molecular enigma of mammalian reproduction.Int J Mol Sci 2014;15:10652-10668[PMID:24933635 DOI:10.3390/ijms150610652]
266 Monk PN,Partridge LJ.Tetraspanins:gateways for infection.Infect Disord Drug Targets 2012;12:4-17[PMID:22034932 DOI:10 .2174/187152612798994957]
267 Thali M.The roles of tetraspanins in HIV-1 replication.Curr Top Microbiol Immunol 2009;339:85-102[PMID:20012525 DOI:10 .1007/978-3-642-02175-6_5]
268 Zhang XA,Huang C.Tetraspanins and cell membrane tubular structures.Cell Mol Life Sci 2012;69:2843-2852[PMID:22450717 DOI:10.1007/s00018-012-0954-0]
269 Conley SM,Stuck MW,Naash MI.Structural and functional relationships between photoreceptor tetraspanins and other superfamily members.Cell Mol Life Sci 2012;69:1035-1047[PMID:21655915 DOI:10.1007/s00018-011-0736-0]
270 Greco C,Bralet MP,Ailane N,Dubart-Kupperschmitt A,Rubinstein E,Le Naour F,Boucheix C.E-cadherin/p120-catenin and tetraspanin Co-029 cooperate for cell motility control in human colon carcinoma.Cancer Res 2010;70:7674-7683[PMID:20858717 DOI:10.1158/0008-5472.CAN-09-4482]
271 Apostolou P,Toloudi M,Ioannou E,Kourtidou E,Chatziioannou M,Kopic A,Komiotis D,Kiritsis C,Manta S,Papasotiriou I.Study of the interaction among Notch pathway receptors,correlation with stemness,as well as their interaction with CD44,dipeptidyl peptidase-IV,hepatocyte growth factor receptor and the SETMAR transferase,in colon cancer stem cells.J Recept Signal Transduct Res 2013;33:353-358[PMID:23964856 DOI:10.3109/10799893.2013.828072]
272 Palagani V,El Khatib M,Kossatz U,Bozko P,Müller MR,Manns MP,Krech T,Malek NP,Plentz RR.Epithelial mesenchymal transition and pancreatic tumor initiating CD44+/Ep CAM+cells are inhibited byγ-secretase inhibitor IX.PLo S One 2012;7:e46514[PMID:23094026 DOI:10.1371/journal.pone.0046514]
273 Philip R,Heiler S,Mu W,Büchler MW,Z?ller M,Thuma F.Claudin-7 promotes the epithelial-mesenchymal transition in human colorectal cancer.Oncotarget 2015;6:2046-2063[PMID:25514462 DOI:10.18632/oncotarget.2858]
274 Sadej R,Grudowska A,Turczyk L,Kordek R,Romanska HM.CD151 in cancer progression and metastasis:a complex scenario.Lab Invest 2014;94:41-51[PMID:24247563 DOI:10.1038/labinvest.2013.136]
275 Ashman L,Z?ller M.Tetraspanin and metastasis.In:Berditchewski F,Rubinstein E,editors.Tetraspanins.Berlin:Springer Verlag,2013:257-298
276 Cruz-Monserrate Z,O’Connor KL.Integrin alpha 6 beta 4promotes migration,invasion through Tiam1 upregulation,and subsequent Rac activation.Neoplasia 2008;10:408-417[PMID:18472958 DOI:10.1593/neo.07868]
277 Cruz-Monserrate Z,Qiu S,Evers BM,O’Connor KL.Upregulation and redistribution of integrin alpha6beta4 expression occurs at an early stage in pancreatic adenocarcinoma progression.Mod Pathol 2007;20:656-667[PMID:17415382 DOI:10.1038/modpathol.3800782]
278 Baril P,Gangeswaran R,Mahon PC,Caulee K,Kocher HM,Harada T,Zhu M,Kalthoff H,Crnogorac-Jurcevic T,Lemoine NR.Periostin promotes invasiveness and resistance of pancreatic cancer cells to hypoxia-induced cell death:role of the beta4 integrin and the PI3k pathway.Oncogene 2007;26:2082-2094[PMID:17043657 DOI:10.1038/sj.onc.1210009]
279 Carpenter BL,Chen M,Knifley T,Davis KA,Harrison SM,Stewart RL,O’Connor KL.Integrinα6β4 Promotes Autocrine Epidermal Growth Factor Receptor(EGFR)Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor(HGF).J Biol Chem 2015;290:27228-27238[PMID:26381405 DOI:10 .1074/jbc.M115.686873]
280 Laval S,Laklai H,Fanjul M,Pucelle M,Laurell H,Billon-Galés A,Le Guellec S,Delisle MB,Sonnenberg A,Susini C,Pyronnet S,Bousquet C.Dual roles of hemidesmosomal proteins in the pancreatic epithelium:the phosphoinositide 3-kinase decides.Oncogene 2014;33:1934-1944[PMID:23624916 DOI:10.1038/onc.2013.146]
281 Giancotti FG.Signal transduction by the alpha 6 beta 4 integrin:charting the path between laminin binding and nuclear events.J Cell Sci 1996;109(Pt 6):1165-1172[PMID:8799807]
282 Yang XH,Flores LM,Li Q,Zhou P,Xu F,Krop IE,Hemler ME.Disruption of laminin-integrin-CD151-focal adhesion kinase axis sensitizes breast cancer cells to Erb B2 antagonists.Cancer Res2010;70:2256-2263[PMID:20197472 DOI:10.1158/0008-5472.CAN-09-4032]
283 Lipscomb EA,Mercurio AM.Mobilization and activation of a signaling competent alpha6beta4integrin underlies its contribution to carcinoma progression.Cancer Metastasis Rev 2005;24:413-423[PMID:16258729]
284 Gagnoux-Palacios L,Dans M,van’t Hof W,Mariotti A,Pepe A,Meneguzzi G,Resh MD,Giancotti FG.Compartmentalization of integrin alpha6beta4 signaling in lipid rafts.J Cell Biol 2003;162:1189-1196[PMID:14517202 DOI:10.1083/jcb.200305006]
285 Yang X,Kovalenko OV,Tang W,Claas C,Stipp CS,Hemler ME.Palmitoylation supports assembly and function of integrintetraspanin complexes.J Cell Biol 2004;167:1231-1240[PMID:15611341 DOI:10.1083/jcb.200404100]
286 Sharma C,Rabinovitz I,Hemler ME.Palmitoylation by DHHC3is critical for the function,expression,and stability of integrinα6β4.Cell Mol Life Sci 2012;69:2233-2244[PMID:22314500DOI:10.1007/s00018-012-0924-6]
287 Germain EC,Santos TM,Rabinovitz I.Phosphorylation of a novel site on the{beta}4 integrin at the trailing edge of migrating cells promotes hemidesmosome disassembly.Mol Biol Cell 2009;20:56-67[PMID:19005215 DOI:10.1091/mbc.E08-06-0646]
288 Frijns E,Sachs N,Kreft M,Wilhelmsen K,Sonnenberg A.EGFinduced MAPK signaling inhibits hemidesmosome formation through phosphorylation of the integrin{beta}4.J Biol Chem2010;285:37650-37662[PMID:20870721 DOI:10.1074/jbc.M110.138818]
289 O’Connor KL,Chen M,Towers LN.Integrinα6β4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated Rho A activation.Am J Physiol Cell Physiol 2012;302:C605-C614[PMID:22049212 DOI:10.1152/ajpcell.00095.2011]
290 Stewart RL,O’Connor KL.Clinical significance of the integrinα6β4 in human malignancies.Lab Invest 2015;95:976-986[PMID:26121317 DOI:10.1038/labinvest.2015.82]
291 Wang H,Leavitt L,Ramaswamy R,Rapraeger AC.Interaction of syndecan and alpha6beta4 integrin cytoplasmic domains:regulation of Erb B2-mediated integrin activation.J Biol Chem2010;285:13569-13579[PMID:20181947 DOI:10.1074/jbc.M110.102137]
292 Chung J,Yoon SO,Lipscomb EA,Mercurio AM.The Met receptor and alpha 6 beta 4 integrin can function independently to promote carcinoma invasion.J Biol Chem 2004;279:32287-32293[PMID:15161909 DOI:10.1074/jbc.M403809200]
293 Wang H,Jin H,Beauvais DM,Rapraeger AC.Cytoplasmic domain interactions of syndecan-1 and syndecan-4 withα6β4integrin mediate human epidermal growth factor receptor(HER1and HER2)-dependent motility and survival.J Biol Chem2014;289:30318-30332[PMID:25202019 DOI:10.1074/jbc.M114.586438]
294 Folgiero V,Avetrani P,Bon G,Di Carlo SE,Fabi A,NisticòC,Vici P,Melucci E,Buglioni S,Perracchio L,Sperduti I,RosanòL,Sacchi A,Mottolese M,Falcioni R.Induction of Erb B-3 expression by alpha6beta4 integrin contributes to tamoxifen resistance in ERbeta1-negative breast carcinomas.PLo S One 2008;3:e1592[PMID:18270579 DOI:10.1371/journal.pone.0001592]
295 Sugiyama H,Mizutani K,Kurita S,Okimoto N,Shimono Y,Takai Y.Interaction of Necl-4/CADM4 with Erb B3 and integrinα6β4and inhibition of Erb B2/Erb B3 signaling and hemidesmosome disassembly.Genes Cells 2013;18:519-528[PMID:23611113DOI:10.1111/gtc.12056]
296 Deng X,Li Q,Hoff J,Novak M,Yang H,Jin H,Erfani SF,Sharma C,Zhou P,Rabinovitz I,Sonnenberg A,Yi Y,Zhou P,Stipp CS,Kaetzel DM,Hemler ME,Yang XH.Integrin-associated CD151drives Erb B2-evoked mammary tumor onset and metastasis.Neoplasia 2012;14:678-689[PMID:22952421 DOI:10.1593/neo.12922]
297 Lipscomb EA,Simpson KJ,Lyle SR,Ring JE,Dugan AS,Mercurio AM.The alpha6beta4 integrin maintains the survival of human breast carcinoma cells in vivo.Cancer Res 2005;65:10970-10976[PMID:16322245 DOI:10.1158/0008-5472.CAN-05-2327]
298 Faure E,Garrouste F,Parat F,Monferran S,Leloup L,Pommier G,Kovacic H,Lehmann M.P2Y2 receptor inhibits EGF-induced MAPK pathway to stabilise keratinocyte hemidesmosomes.J Cell Sci 2012;125:4264-4277[PMID:22718344 DOI:10.1242/jcs.097600]
299 Bhatia V,Mula RV,Weigel NL,Falzon M.Parathyroid hormonerelated protein regulates cell survival pathways via integrin alpha6beta4-mediated activation of phosphatidylinositol 3-kinase/Akt signaling.Mol Cancer Res 2009;7:1119-1131[PMID:19584267 DOI:10.1158/1541-7786.MCR-08-0568]
300 Mercurio AM,Bachelder RE,Bates RC,Chung J.Autocrine signaling in carcinoma:VEGF and the alpha6beta4 integrin.Semin Cancer Biol 2004;14:115-122[PMID:15018895 DOI:10.1016/j.semcancer.2003.09.016]
301 Serini G,Valdembri D,Bussolino F.Integrins and angiogenesis:a sticky business.Exp Cell Res 2006;312:651-658[PMID:16325811 DOI:10.1016/j.yexcr.2005.10.020]
302 Chen M,Sinha M,Luxon BA,Bresnick AR,O’Connor KL.Integrin alpha6beta4 controls the expression of genes associated with cell motility,invasion,and metastasis,including S100A4/metastasin.J Biol Chem 2009;284:1484-1494[PMID:19011242DOI:10.1074/jbc.M803997200]
303 Soung YH,Gil HJ,Clifford JL,Chung J.Role ofα6β4 integrin in cell motility,invasion and metastasis of mammary tumors.Curr Protein Pept Sci 2011;12:23-29[PMID:21190525 DOI:10.2174/138920311795659399]
304 Vieira AF,Ribeiro AS,Dionísio MR,Sousa B,Nobre AR,Albergaria A,Santiago-Gómez A,Mendes N,Gerhard R,Schmitt F,Clarke RB,Paredes J.P-cadherin signals through the laminin receptorα6β4 integrin to induce stem cell and invasive properties in basal-like breast cancer cells.Oncotarget 2014;5:679-692[PMID:24553076 DOI:10.18632/oncotarget.1459]
305 Wicha MS.B4 androgen ablation:attacking the prostate cancer stem cell.J Clin Invest 2013;123:563-565[PMID:23348735DOI:10.1172/JCI67460]
306 Yin Y,Deng X,Liu Z,Baldwin LA,Lefringhouse J,Zhang J,Hoff JT,Erfani SF,Rucker EB,O’Connor K,Liu C,Wu Y,Zhou BP,Yang XH.CD151 represses mammary gland development by maintaining the niches of progenitor cells.Cell Cycle 2014;13:2707-2722[PMID:25486358 DOI:10.4161/15384101.2015.945823]
307 Ramsey DM,Mc Alpine SR.Halting metastasis through CXCR4inhibition.Bioorg Med Chem Lett 2013;23:20-25[PMID:23211868 DOI:10.1016/j.bmcl.2012.10.138]
308 Hermann PC,Huber SL,Herrler T,Aicher A,Ellwart JW,Guba M,Bruns CJ,Heeschen C.Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer.Cell Stem Cell 2007;1:313-323[PMID:18371365 DOI:10.1016/j.stem.2007.06.002]
309 Du H,Bennett D,Li L,Whitlock G,Guo Y,Collins R,Chen J,Bian Z,Hong LS,Feng S,Chen X,Chen L,Zhou R,Mao E,Peto R,Chen Z.Physical activity and sedentary leisure time and their associations with BMI,waist circumference,and percentage body fat in 0.5 million adults:the China Kadoorie Biobank study.Am J Clin Nutr 2013;97:487-496[PMID:23364014 DOI:10.3945/ajcn.112.046854]
310 Bertolini G,D’Amico L,Moro M,Landoni E,Perego P,Miceli R,Gatti L,Andriani F,Wong D,Caserini R,Tortoreto M,Milione M,Ferracini R,Mariani L,Pastorino U,Roato I,Sozzi G,Roz L.Microenvironment-Modulated Metastatic CD133+/CXCR4+/Ep CAM-Lung Cancer-Initiating Cells Sustain Tumor Dissemination and Correlate with Poor Prognosis.Cancer Res2015;75:3636-3649[PMID:26141860 DOI:10.1158/0008-5472.CAN-14-3781]
311 Nagasawa T.CXC chemokine ligand 12(CXCL12)and its receptor CXCR4.J Mol Med(Berl)2014;92:433-439[PMID:24722947 DOI:10.1007/s00109-014-1123-8]
312 Trautmann F,Cojoc M,Kurth I,Melin N,Bouchez LC,Dubrovska A,Peitzsch C.CXCR4 as biomarker for radioresistant cancer stem cells.Int J Radiat Biol 2014;90:687-699[PMID:24650104 DOI:10.3109/09553002.2014.906766]
313 Chatterjee S,Behnam Azad B,Nimmagadda S.The intricate role of CXCR4 in cancer.Adv Cancer Res 2014;124:31-82[PMID:25287686 DOI:10.1016/B978-0-12-411638-2.00002-1]
314 Shi J,Wei Y,Xia J,Wang S,Wu J,Chen F,Huang G,Chen J.CXCL12-CXCR4 contributes to the implication of bone marrow in cancer metastasis.Future Oncol 2014;10:749-759[PMID:24799056 DOI:10.2217/fon.13.193]
315 Maréchal R,Demetter P,Nagy N,Berton A,Decaestecker C,Polus M,Closset J,Devière J,Salmon I,Van Laethem JL.High expression of CXCR4 may predict poor survival in resected pancreatic adenocarcinoma.Br J Cancer 2009;100:1444-1451[PMID:19352387 DOI:10.1038/sj.bjc.6605020]
316 Bachet JB,Maréchal R,Demetter P,Bonnetain F,Couvelard A,Svrcek M,Bardier-Dupas A,Hammel P,Sauvanet A,Louvet C,Paye F,Rougier P,Penna C,Vaillant JC,AndréT,Closset J,Salmon I,Emile JF,Van Laethem JL.Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma.Ann Oncol 2012;23:2327-2335[PMID:22377565 DOI:10.1093/annonc/mdr617]
317 Chinni SR,Yamamoto H,Dong Z,Sabbota A,Bonfil RD,Cher ML.CXCL12/CXCR4 transactivates HER2 in lipid rafts of prostate cancer cells and promotes growth of metastatic deposits in bone.Mol Cancer Res 2008;6:446-457[PMID:18337451 DOI:10 .1158/1541-7786]
318 Ho TK,Shiwen X,Abraham D,Tsui J,Baker D.StromalCell-Derived Factor-1(SDF-1)/CXCL12 as Potential Target of Therapeutic Angiogenesis in Critical Leg Ischaemia.Cardiol R e s P r a c t 2 0 1 2;2 0 1 2:143209[PMID:22462026 DOI:10 .1155/2012/143209]
319 Arjonen A,Kaukonen R,Ivaska J.Filopodia and adhesion in cancer cell motility.Cell Adh Migr 2011;5:421-430[PMID:21975551 DOI:10.4161/cam.5.5.17723]
320 Liao Y,Hung MC.Physiological regulation of Akt activity and stability.Am J Transl Res 2010;2:19-42[PMID:20182580]
321 Mo W,Chen J,Patel A,Zhang L,Chau V,Li Y,Cho W,Lim K,Xu J,Lazar AJ,Creighton CJ,Bolshakov S,Mc Kay RM,Lev D,Le LQ,Parada LF.CXCR4/CXCL12 mediate autocrine cellcycle progression in NF1-associated malignant peripheral nerve sheath tumors.Cell 2013;152:1077-1090[PMID:23434321 DOI:10 .1016/j.cell.2013.01.053]
322 Zoughlami Y,Voermans C,Brussen K,van Dort KA,Kootstra NA,Maussang D,Smit MJ,Hordijk PL,van Hennik PB.Regulation of CXCR4 conformation by the small GTPase Rac1:implications for HIV infection.Blood 2012;119:2024-2032[PMID:22238325 DOI:10.1182/blood-2011-06-364828]
323 Drury LJ,Ziarek JJ,Gravel S,Veldkamp CT,Takekoshi T,Hwang ST,Heveker N,Volkman BF,Dwinell MB.Monomeric and dimeric CXCL12 inhibit metastasis through distinct CXCR4 interactions and signaling pathways.Proc Natl Acad Sci USA 2011;108:17655-17660[PMID:21990345 DOI:10.1073/pnas.1101133108]
324 Sotillos S,Díaz-Meco MT,Moscat J,Castelli-Gair Hombría J.Polarized subcellular localization of Jak/STAT components is required for efficient signaling.Curr Biol 2008;18:624-629[PMID:18424141 DOI:10.1016/j.cub.2008.03.055]
325 Bao W,Fu HJ,Xie QS,Wang L,Zhang R,Guo ZY,Zhao J,Meng YL,Ren XL,Wang T,Li Q,Jin BQ,Yao LB,Wang RA,Fan DM,Chen SY,Jia LT,Yang AG.HER2 interacts with CD44 to upregulate CXCR4 via epigenetic silencing of micro RNA-139 in gastric cancer cells.Gastroenterology 2011;141:2076-2087.e6[PMID:21925125 DOI:10.1053/j.gastro.2011.08.050]
326 Arnaud MP,Vallée A,Robert G,Bonneau J,Leroy C,VarinBlank N,Rio AG,Troadec MB,Galibert MD,Gandemer V.CD9,a key actor in the dissemination of lymphoblastic leukemia,modulating CXCR4-mediated migration via RAC1 signaling.Blood 2015;126:1802-1812[PMID:26320102 DOI:10.1182/blood-2015-02-628560]
327 Desterke C,Martinaud C,Guerton B,Pieri L,Bogani C,Clay D,Torossian F,Lataillade JJ,Hasselbach HC,Gisslinger H,Demory JL,Dupriez B,Boucheix C,Rubinstein E,Amsellem S,Vannucchi AM,Le Bousse-Kerdilès MC.Tetraspanin CD9participates in dysmegakaryopoiesis and stromal interactions in primary myelofibrosis.Haematologica 2015;100:757-767[PMID:25840601 DOI:10.3324/haematol.2014.118497]
328 Zhang Y,Foudi A,Geay JF,Berthebaud M,Buet D,Jarrier P,Jalil A,Vainchenker W,Louache F.Intracellular localization and constitutive endocytosis of CXCR4 in human CD34+hematopoietic progenitor cells.Stem Cells 2004;22:1015-1029[PMID:15536192 DOI:10.1634/stemcells.22-6-1015]
329 Wang X,Ding X,Nan L,Wang Y,Wang J,Yan Z,Zhang W,Sun J,Zhu W,Ni B,Dong S,Yu L.Investigation of the roles of exosomes in colorectal cancer liver metastasis.Oncol Rep 2015;33:2445-2453[PMID:25760247 DOI:10.3892/or.2015.3843]
330 Munz M,Baeuerle PA,Gires O.The emerging role of Ep CAM in cancer and stem cell signaling.Cancer Res 2009;69:5627-5629[PMID:19584271 DOI:10.1158/0008-5472.CAN-09-0654]
331 Marhaba R,Klingbeil P,Nuebel T,Nazarenko I,Buechler MW,Zoeller M.CD44 and Ep CAM:cancer-initiating cell markers.Curr Mol Med 2008;8:784-804[PMID:19075676 DOI:10.2174/156652408786733667]
332 Keysar SB,Jimeno A.More than markers:biological significance of cancer stem cell-defining molecules.Mol Cancer Ther 2010;9:2450-2457[PMID:20716638 DOI:10.1158/1535-7163.MCT-10-0530]
333 Patriarca C,Macchi RM,Marschner AK,Mellstedt H.Epithelial cell adhesion molecule expression(CD326)in cancer:a short review.Cancer Treat Rev 2012;38:68-75[PMID:21576002 DOI:10 .1016/j.ctrv.2011.04.002]
334 Gires O.Lessons from common markers of tumor-initiating cells in solid cancers.Cell Mol Life Sci 2011;68:4009-4022[PMID:21786143 DOI:10.1007/s00018-011-0772-9]
335 Imrich S,Hachmeister M,Gires O.Ep CAM and its potential role in tumor-initiating cells.Cell Adh Migr 2012;6:30-38[PMID:22647938 DOI:10.4161/cam.18953]
336 DolléL,Theise ND,Schmelzer E,Boulter L,Gires O,van Grunsven LA.Ep CAM and the biology of hepatic stem/progenitor cells.Am J Physiol Gastrointest Liver Physiol 2015;308:G233-G250[PMID:25477371 DOI:10.1152/ajpgi.00069.2014]
337 Le Naour F,Zoller M.The tumor antigen Ep CAM:tetraspanins and the tight junction protein claudin-7,new partners,new functions.Front Biosci 2008;13:5847-5865[PMID:18508627]
338 Ladwein M,Pape UF,Schmidt DS,Schn?lzer M,Fiedler S,Langbein L,Franke WW,Moldenhauer G,Z?ller M.The cellcell adhesion molecule Ep CAM interacts directly with the tight junction protein claudin-7.Exp Cell Res 2005;309:345-357[PMID:16054130 DOI:10.1016/j.yexcr.2005.06.013]
339 Wu CJ,Mannan P,Lu M,Udey MC.Epithelial cell adhesion molecule(Ep CAM)regulates claudin dynamics and tight junctions.J Biol Chem 2013;288:12253-12268[PMID:23486470 DOI:10 .1074/jbc.M113.457499]
340 Okada T,Nakamura T,Watanabe T,Onoda N,Ashida A,Okuyama R,Ito K.Coexpression of Ep CAM,CD44 variant isoforms and claudin-7 in anaplastic thyroid carcinoma.PLo S One 2014;9:e94487[PMID:24727741 DOI:10.1371/journal.pone.0094487]
341 Thuma F,Z?ller M.Ep CAM-associated claudin-7 supports lymphatic spread and drug resistance in rat pancreatic cancer.Int J Cancer 2013;133:855-866[PMID:23390083 DOI:10.1002/ijc.28085]
342 Balzar M,Briaire-de Bruijn IH,Rees-Bakker HA,Prins FA,Helfrich W,de Leij L,Riethmüller G,Alberti S,Warnaar SO,Fleuren GJ,Litvinov SV.Epidermal growth factor-like repeats mediate lateral and reciprocal interactions of Ep-CAM molecules in homophilic adhesions.Mol Cell Biol 2001;21:2570-2580[PMID:11259604 DOI:10.1128/MCB.21.7.2570-2580.2001]
343 Winter MJ,Nagelkerken B,Mertens AE,Rees-Bakker HA,Briaire-de Bruijn IH,Litvinov SV.Expression of Ep-CAM shifts the state of cadherin-mediated adhesions from strong to weak.Exp Cell Res 2003;285:50-58[PMID:12681286 DOI:10.1016/S0014-4827(02)00045-9]
344 Yamashita T,Budhu A,Forgues M,Wang XW.Activation of hepatic stem cell marker Ep CAM by Wnt-beta-catenin signaling in hepatocellular carcinoma.Cancer Res 2007;67:10831-10839[PMID:18006828 DOI:10.1158/0008-5472.CAN-07-0908]
345 Lu H,Ma J,Yang Y,Shi W,Luo L.Ep CAM is an endodermspecific Wnt derepressor that licenses hepatic development.Dev Cell 2013;24:543-553[PMID:23484855 DOI:10.1016/j.devcel.2013.01.021]
346 Maghzal N,Vogt E,Reintsch W,Fraser JS,Fagotto F.The tumorassociated Ep CAM regulates morphogenetic movements through intracellular signaling.J Cell Biol 2010;191:645-659[PMID:20974811 DOI:10.1083/jcb.201004074]
347 Denzel S,Mack B,Eggert C,Massoner P,St?cklein N,Kemming D,Harréus U,Gires O.MMP7 is a target of the tumour-associated antigen Ep CAM.Int J Exp Pathol 2012;93:341-353[PMID:22974215 DOI:10.1111/j.1365-2613.2012.00826.x]
348 Sankpal NV,Willman MW,Fleming TP,Mayfield JD,Gillanders WE.Transcriptional repression of epithelial cell adhesion molecule contributes to p53 control of breast cancer invasion.Cancer Res2009;69:753-757[PMID:19141643 DOI:10.1158/0008-5472.CAN-08-2708]
349 Maetzel D,Denzel S,Mack B,Canis M,Went P,Benk M,Kieu C,Papior P,Baeuerle PA,Munz M,Gires O.Nuclear signalling by tumour-associated antigen Ep CAM.Nat Cell Biol 2009;11:162-171[PMID:19136966 DOI:10.1038/ncb1824]
350 Lin CW,Liao MY,Lin WW,Wang YP,Lu TY,Wu HC.Epithelial cell adhesion molecule regulates tumor initiation and tumorigenesis via activating reprogramming factors and epithelial-mesenchymal transition gene expression in colon cancer.J Biol Chem 2012;287:39449-39459[PMID:22989882 DOI:10.1074/jbc.M112.386235]
351 Yovchev MI,Grozdanov PN,Zhou H,Racherla H,Guha C,Dabeva MD.Identification of adult hepatic progenitor cells capable of repopulating injured rat liver.Hepatology 2008;47:636-647[PMID:18023068 DOI:10.1002/hep.22047]
352 Lei Z,Maeda T,Tamura A,Nakamura T,Yamazaki Y,Shiratori H,Yashiro K,Tsukita S,Hamada H.Ep CAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins.Dev Biol 2012;371:136-145[PMID:22819673DOI:10.1016/j.ydbio.2012.07.005]
353 Schneeberger EE,Lynch RD.The tight junction:a multifunctional complex.Am J Physiol Cell Physiol 2004;286:C1213-C1228[PMID:15151915 DOI:10.1152/ajpcell.00558.2003]
354 Lal-Nag M,Morin PJ.The claudins.Genome Biol 2009;10:235[PMID:19706201 DOI:10.1186/gb-2009-10-8-235]
355 Krug SM,Schulzke JD,Fromm M.Tight junction,selective permeability,and related diseases.Semin Cell Dev Biol 2014;36:166-176[PMID:25220018 DOI:10.1016/j.semcdb.2014.09.002]
356 Ding L,Lu Z,Foreman O,Tatum R,Lu Q,Renegar R,Cao J,Chen YH.Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice.Gastroenterology 2012;142:305-315[PMID:22044670 DOI:10.1053/j.gastro.2011.10.025]
357 Tanaka H,Takechi M,Kiyonari H,Shioi G,Tamura A,Tsukita S.Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice.Gut 2015;64:1529-1538[PMID:25691495 DOI:10.1136/gutjnl-2014-308419]
358 Van Itallie CM,Anderson JM.Claudin interactions in and out of the tight junction.Tissue Barriers 2013;1:e25247[PMID:24665401 DOI:10.4161/tisb.25247]
359 Findley MK,Koval M.Regulation and roles for claudin-family tight junction proteins.IUBMB Life 2009;61:431-437[PMID:19319969 DOI:10.1002/iub.175]
360 Gonzalez-Mariscal L,Namorado Mdel C,Martin D,Sierra G,Reyes JL.The tight junction proteins claudin-7 and-8 display a different subcellular localization at Henle’s loops and collecting ducts of rabbit kidney.Nephrol Dial Transplant 2006;21:2391-2398[PMID:16766545 DOI:10.1093/ndt/gfl255]
361 Tauro BJ,Greening DW,Mathias RA,Mathivanan S,Ji H,Simpson RJ.Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids.Mol Cell Proteomics 2013;12:587-598[PMID:23230278 DOI:10.1074/mcp.M112.021303]
362 Lu Z,Kim do H,Fan J,Lu Q,Verbanac K,Ding L,Renegar R,Chen YH.A non-tight junction function of claudin-7-Interaction with integrin signaling in suppressing lung cancer cell proliferation and detachment.Mol Cancer 2015;14:120[PMID:26081244DOI:10.1186/s12943-015-0387-0]
363 D’Souza T,Agarwal R,Morin PJ.Phosphorylation of claudin-3at threonine 192 by c AMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells.J Biol Chem2005;280:26233-26240[PMID:15905176 DOI:10.1074/jbc.M502003200]
364 French AD,Fiori JL,Camilli TC,Leotlela PD,O’Connell MP,Frank BP,Subaran S,Indig FE,Taub DD,Weeraratna AT.PKC and PKA phosphorylation affect the subcellular localization of claudin-1 in melanoma cells.Int J Med Sci 2009;6:93-101[PMID:19305641 DOI:10.7150/ijms.6.93]
365 Chen C,Wang P,Su Q,Wang S,Wang F.Myosin light chain kinase mediates intestinal barrier disruption following burn injury.PLo S One 2012;7:e34946[PMID:22529961 DOI:10.1371/journal.pone.0034946]
366 Nishida M,Yoshida M,Nishiumi S,Furuse M,Azuma T.Claudin-2 regulates colorectal inflammation via myosin light chain kinase-dependent signaling.Dig Dis Sci 2013;58:1546-1559[PMID:23306855 DOI:10.1007/s10620-012-2535-3]
367 Ikari A,Ito M,Okude C,Sawada H,Harada H,Degawa M,Sakai H,Takahashi T,Sugatani J,Miwa M.Claudin-16 is directly phosphorylated by protein kinase A independently of a vasodilatorstimulated phosphoprotein-mediated pathway.J Cell Physiol 2008;214:221-229[PMID:17559069 DOI:10.1002/jcp.21178]
368 Li X,Akhtar S,Choudhry MA.Alteration in intestine tight junction protein phosphorylation and apoptosis is associated with increase in IL-18 levels following alcohol intoxication and burn injury.Biochim Biophys Acta 2012;1822:196-203[PMID:22001439DOI:10.1016/j.bbadis.2011.09.019]
369 Shen L.Tight junctions on the move:molecular mechanisms for epithelial barrier regulation.Ann N Y Acad Sci 2012;1258:9-18[PMID:22731710 DOI:10.1111/j.1749-6632.2012.06613.x]
370 Sj?A,Magnusson KE,Peterson KH.Protein kinase C activation has distinct effects on the localization,phosphorylation and detergent solubility of the claudin protein family in tight and leaky epithelial cells.J Membr Biol 2010;236:181-189[PMID:20697888 DOI:10.1007/s00232-010-9289-7]
371 Heiler S,Mu W,Z?ller M,Thuma F.The importance of claudin-7palmitoylation on membrane subdomain localization and metastasis-promoting activities.Cell Commun Signal 2015;13:29[PMID:26054340 DOI:10.1186/s12964-015-0105-y]
372 Nübel T,Preobraschenski J,Tuncay H,Weiss T,Kuhn S,Ladwein M,Langbein L,Z?ller M.Claudin-7 regulates Ep CAM-mediated functions in tumor progression.Mol Cancer Res 2009;7:285-299[PMID:19276185 DOI:10.1158/1541-7786.MCR-08-0200]
373 Levental I,Grzybek M,Simons K.Greasing their way:lipid modifications determine protein association with membrane rafts.Biochemistry 2010;49:6305-6316[PMID:20583817 DOI:10 .1021/bi100882y]
374 Stepanek O,Draber P,Horejsi V.Palmitoylated transmembrane adaptor proteins in leukocyte signaling.Cell Signal 2014;26:895-902[PMID:24440308 DOI:10.1016/j.cellsig.2014.01.007]
375 Head BP,Patel HH,Insel PA.Interaction of membrane/lipid rafts with the cytoskeleton:impact on signaling and function:membrane/lipid rafts,mediators of cytoskeletal arrangement and cell signaling.Biochim Biophys Acta 2014;1838:532-545[PMID:23899502 DOI:10.1016/j.bbamem.2013.07.018]
376 Mollinedo F,Gajate C.Lipid rafts as major platforms for signaling regulation in cancer.Adv Biol Regul 2015;57:130-146[PMID:25465296 DOI:10.1016/j.jbior.2014.10.003]
377 Thiel KW,Carpenter G.Erb B-4 and TNF-alpha converting enzyme localization to membrane microdomains.Biochem Biophys Res Commun 2006;350:629-633[PMID:17027649 DOI:10 .1016/j.bbrc.2006.09.095]
378 Vetrivel KS,Cheng H,Kim SH,Chen Y,Barnes NY,Parent AT,Sisodia SS,Thinakaran G.Spatial segregation of gamma-secretase and substrates in distinct membrane domains.J Biol Chem2005;280:25892-25900[PMID:15886206 DOI:10.1074/jbc.M503570200]
379 Cheng JM,Volk L,Janaki DK,Vyakaranam S,Ran S,Rao KA.Tumor suppressor function of Rab25 in triple-negative breast cancer.Int J Cancer 2010;126:2799-2812[PMID:19795443DOI:10.1002/ijc.24900]
380 Nicolson GL.Cell membrane fluid-mosaic structure and cancer metastasis.Cancer Res 2015;75:1169-1176[PMID:25788696DOI:10.1158/0008-5472.CAN-14-3216]
381 Ren F,Sheng WQ,Du X.CD133:a cancer stem cells marker,is used in colorectal cancers.World J Gastroenterol 2013;19:2603-2611[PMID:23674867 DOI:10.3748/wjg.v19.i17.2603]
382 Grosse-Gehling P,Fargeas CA,Dittfeld C,Garbe Y,Alison MR,Corbeil D,Kunz-Schughart LA.CD133 as a biomarker for putative cancer stem cells in solid tumours:limitations,problems and challenges.J Pathol 2013;229:355-378[PMID:22899341 DOI:10 .1002/path.4086]
383 Yiming L,Yunshan G,Bo M,Yu Z,Tao W,Gengfang L,Dexian F,Shiqian C,Jianli J,Juan T,Zhinan C.CD133 overexpression correlates with clinicopathological features of gastric cancer patients and its impact on survival:a systematic review and metaanalysis.Oncotarget 2015;6:42019-42027[PMID:26503471DOI:10.18632/oncotarget.5714]
384 Wu Y,Wu PY.CD133 as a marker for cancer stem cells:progresses and concerns.Stem Cells Dev 2009;18:1127-1134[PMID:19409053 DOI:10.1089/scd.2008.0338]
385 Li X,Zhao H,Gu J,Zheng L.Prognostic value of cancer stem cell marker CD133 expression in pancreatic ductal adenocarcinoma(PDAC):a systematic review and meta-analysis.Int J Clin Exp Pathol 2015;8:12084-12092[PMID:26722393]
386 Xu L.Cancer stem cell in the progression and therapy of pancreatic cancer.Front Biosci(Landmark Ed)2013;18:795-802[PMID:23747847]
387 Zhu H,Wang D,Zhang L,Xie X,Wu Y,Liu Y,Shao G,Su Z.Upregulation of autophagy by hypoxia-inducible factor-1αpromotes EMT and metastatic ability of CD133+pancreatic cancer stem-like cells during intermittent hypoxia.Oncol Rep 2014;32:935-942[PMID:24994549 DOI:10.3892/or.2014.3298]
388 Hou YC,Chao YJ,Tung HL,Wang HC,Shan YS.Coexpression of CD44-positive/CD133-positive cancer stem cells and CD204-positive tumor-associated macrophages is a predictor of survival in pancreatic ductal adenocarcinoma.Cancer 2014;120:2766-2777[PMID:24839953 DOI:10.1002/cncr.28774]
389 Banerjee S,Nomura A,Sangwan V,Chugh R,Dudeja V,Vickers SM,Saluja A.CD133+tumor initiating cells in a syngenic murine model of pancreatic cancer respond to Minnelide.Clin Cancer Res2014;20:2388-2399[PMID:24634377 DOI:10.1158/1078-0432.CCR-13-2947]
390 Olempska M,Eisenach PA,Ammerpohl O,Ungefroren H,Fandrich F,Kalthoff H.Detection of tumor stem cell markers in pancreatic carcinoma cell lines.Hepatobiliary Pancreat Dis Int2007;6:92-97[PMID:17287174]
391 Yin AH,Miraglia S,Zanjani ED,Almeida-Porada G,Ogawa M,Leary AG,Olweus J,Kearney J,Buck DW.AC133,a novel marker for human hematopoietic stem and progenitor cells.Blood 1997;90:5002-5012[PMID:9389720]
392 Weigmann A,Corbeil D,Hellwig A,Huttner WB.Prominin,a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells,is targeted to plasmalemmal protrusions of non-epithelial cells.Proc Natl Acad Sci USA 1997;94:12425-12430[PMID:9356465]
393 Liu J,Mao Z,Huang J,Xie S,Liu T,Mao Z.Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy.Biochem Biophys Res Commun 2014;444:670-675[PMID:24502949 DOI:10.1016/j.bbrc.2014.01.164]
394 Liu YP,Yang CJ,Huang MS,Yeh CT,Wu AT,Lee YC,Lai TC,Lee CH,Hsiao YW,Lu J,Shen CN,Lu PJ,Hsiao M.Cisplatin selects for multidrug-resistant CD133+cells in lung adenocarcinoma by activating Notch signaling.Cancer Res2013;73:406-416[PMID:23135908 DOI:10.1158/0008-5472.CAN-12-1733]
395 Jeng KS,Sheen IS,Jeng WJ,Yu MC,Hsiau HI,Chang FY,Tsai HH.Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive cells of mouse liver cancer Hepa 1-6 cells.Onco Targets Ther 2013;6:1047-1055[PMID:23950652 DOI:10 .2147/OTT.S44828]
396 Ma S.Biology and clinical implications of CD133(+)liver cancer stem cells.Exp Cell Res 2013;319:126-132[PMID:22999864DOI:10.1016/j.yexcr.2012.09.007]
397 Fargeas CA,KarbanováJ,Jászai J,Corbeil D.CD133 and membrane microdomains:old facets for future hypotheses.World J Gastroenterol 2011;17:4149-4152[PMID:22039332 DOI:10 .3748/wjg.v17.i36.4149]
398 Jiang W,Zhang Y,Kane KT,Collins MA,Simeone DM,di Magliano MP,Nguyen KT.CD44 regulates pancreatic cancer invasion through MT1-MMP.Mol Cancer Res 2015;13:9-15[PMID:25566991 DOI:10.1158/1541-7786.MCR-14-0076]
399 Preca BT,Bajdak K,Mock K,Sundararajan V,Pfannstiel J,Maurer J,Wellner U,Hopt UT,Brummer T,Brabletz S,Brabletz T,Stemmler MP.A self-enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells.Int J Cancer 2015;137:2566-2577[PMID:26077342 DOI:10.1002/ijc.29642]
400 Chanmee T,Ontong P,Mochizuki N,Kongtawelert P,Konno K,Itano N.Excessive hyaluronan production promotes acquisition of cancer stem cell signatures through the coordinated regulation of Twist and the transforming growth factorβ(TGF-β)-Snail signaling axis.J Biol Chem 2014;289:26038-26056[PMID:25077968 DOI:10.1074/jbc.M114.564120]
401 Chung SS,Aroh C,Vadgama JV.Constitutive activation of STAT3signaling regulates h TERT and promotes stem cell-like traits in human breast cancer cells.PLo S One 2013;8:e83971[PMID:24386318 DOI:10.1371/journal.pone.0083971]
402 Bao B,Wang Z,Ali S,Kong D,Li Y,Ahmad A,Banerjee S,Azmi AS,Miele L,Sarkar FH.Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells.Cancer Lett 2011;307:26-36[PMID:21463919 DOI:10 .1016/j.canlet.2011.03.012]
403 De Falco V,Tamburrino A,Ventre S,Castellone MD,Malek M,ManiéSN,Santoro M.CD44 proteolysis increases CREB phosphorylation and sustains proliferation of thyroid cancer cells.Cancer Res 2012;72:1449-1458[PMID:22271686 DOI:10 .1158/0008-5472.CAN-11-3320]
404 Lee D,Na J,Ryu J,Kim HJ,Nam SH,Kang M,Jung JW,Lee MS,Song HE,Choi J,Lee GH,Kim TY,Chung JK,Park KH,Kim SH,Kim H,Seo H,Kim P,Youn H,Lee JW.Interaction of tetraspan(in)TM4SF5 with CD44 promotes self-renewal and circulating capacities of hepatocarcinoma cells.Hepatology 2015;61:1978-1997[PMID:25627085 DOI:10.1002/hep.27721]
405 Ju SY,Chiou SH,Su Y.Maintenance of the stemness in CD44(+)HCT-15 and HCT-116 human colon cancer cells requires mi R-203suppression.Stem Cell Res 2014;12:86-100[PMID:24145190DOI:10.1016/j.scr.2013.09.011]
406 S u Y J,Lai HM,Chang YW,Chen GY,Lee JL.Direct reprogramming of stem cell properties in colon cancer cells by CD44.EMBO J 2011;30:3186-3199[PMID:21701559 DOI:10 .1038/emboj.2011.211]
407 Kang M,Choi S,Jeong SJ,Lee SA,Kwak TK,Kim H,Jung O,Lee MS,Ko Y,Ryu J,Choi YJ,Jeong D,Lee HJ,Ye SK,Kim SH,Lee JW.Cross-talk between TGFβ1 and EGFR signalling pathways induces TM4SF5 expression and epithelial-mesenchymal transition.Biochem J 2012;443:691-700[PMID:22292774 DOI:10 .1042/BJ20111584]
408 Lee SA,Lee SY,Cho IH,Oh MA,Kang ES,Kim YB,Seo WD,Choi S,Nam JO,Tamamori-Adachi M,Kitajima S,Ye SK,Kim S,Hwang YJ,Kim IS,Park KH,Lee JW.Tetraspanin TM4SF5mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma.J Clin Invest 2008;118:1354-1366[PMID:18357344 DOI:10.1172/JCI33768]
409 Lee KH,Ahn EJ,Oh SJ,Kim O,Joo YE,Bae JA,Yoon S,Ryu HH,Jung S,Kim KK,Lee JH,Moon KS.KITENIN promotes glioma invasiveness and progression,associated with the induction of EMT and stemness markers.Oncotarget 2015;6:3240-3253[PMID:25605251]
410 D’Angelo RC,Liu XW,Najy AJ,Jung YS,Won J,Chai KX,Fridman R,Kim HR.TIMP-1 via TWIST1 induces EMT phenotypes in human breast epithelial cells.Mol Cancer Res2014;12:1324-1333[PMID:24895412 DOI:10.1158/1541-7786.MCR-14-0105]
411 Baldwin LA,Hoff JT,Lefringhouse J,Zhang M,Jia C,Liu Z,Erfani S,Jin H,Xu M,She QB,van Nagell JR,Wang C,Chen L,Plattner R,Kaetzel DM,Luo J,Lu M,West D,Liu C,Ueland FR,Drapkin R,Zhou BP,Yang XH.CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling.Oncotarget 2014;5:12203-12217[PMID:25356755]
412 Lupia A,Peppicelli S,Witort E,Bianchini F,Carloni V,Pimpinelli N,Urso C,Borgognoni L,Capaccioli S,Calorini L,Lulli M.CD63tetraspanin is a negative driver of epithelial-to-mesenchymal transition in human melanoma cells.J Invest Dermatol 2014;134:2947-2956[PMID:24940653 DOI:10.1038/jid.2014.258]
413 Sobolik T,Su YJ,Wells S,Ayers GD,Cook RS,Richmond A.CXCR4 drives the metastatic phenotype in breast cancer through induction of CXCR2 and activation of MEK and PI3K pathways.Mol Biol Cell 2014;25:566-582[PMID:24403602 DOI:10.1091/mbc.E13-07-0360]
414 Jung YD,Shim JW,Park SJ,Choi SH,Yang K,Heo K,Park MT.Downregulation of UHRF1 promotes EMT via inducing CXCR4in human cancer cells.Int J Oncol 2015;46:1232-1242[PMID:25572953 DOI:10.3892/ijo.2014.2813]
415 Gao J,Yan Q,Wang J,Liu S,Yang X.Epithelial-to-mesenchymal transition induced by TGF-β1 is mediated by AP1-dependent Ep CAM expression in MCF-7 cells.J Cell Physiol 2015;230:775-782[PMID:25205054 DOI:10.1002/jcp.24802]
416 Massoner P,Thomm T,Mack B,Untergasser G,Martowicz A,Bobowski K,Klocker H,Gires O,Puhr M.Ep CAM is overexpressed in local and metastatic prostate cancer,suppressed by chemotherapy and modulated by MET-associated mi RNA-200 c/205.Br J Cancer 2014;111:955-964[PMID:24992580DOI:10.1038/bjc.2014.366]
417 Bhat AA,Pope JL,Smith JJ,Ahmad R,Chen X,Washington MK,Beauchamp RD,Singh AB,Dhawan P.Claudin-7 expression induces mesenchymal to epithelial transformation(MET)to inhibit colon tumorigenesis.Oncogene 2015;34:4570-4580[PMID:25500541 DOI:10.1038/onc.2014.385]
418 Nomura A,Banerjee S,Chugh R,Dudeja V,Yamamoto M,Vickers SM,Saluja AK.CD133 initiates tumors,induces epithelialmesenchymal transition and increases metastasis in pancreatic cancer.Oncotarget 2015;6:8313-8322[PMID:25829252]
419 Yu Z,Pestell TG,Lisanti MP,Pestell RG.Cancer stem cells.Int J Biochem Cell Biol 2012;44:2144-2151[PMID:22981632 DOI:10 .1016/j.biocel.2012.08.022]
420 Mimeault M,Batra SK.Molecular biomarkers of cancer stem/progenitor cells associated with progression,metastases,and treatment resistance of aggressive cancers.Cancer Epidemiol Biomarkers Prev 2014;23:234-254[PMID:24273063 DOI:10 .1158/1055-9965.EPI-13-0785]
421 Zaravinos A.The Regulatory Role of Micro RNAs in EMT and Cancer.J Oncol 2015;2015:865816[PMID:25883654 DOI:10 .1155/2015/865816]
422 Hu Y,Tang H.Micro RNAs regulate the epithelial to mesenchymal transition(EMT)in cancer progression.Microrna 2014;3:108-117[PMID:25323025]
423 Bourguignon LY.Hyaluronan-CD44 interaction promotes micro RNA signaling and Rho GTPase activation leading to tumor progression.Small GTPases 2012;3:53-59[PMID:22714418DOI:10.4161/sgtp.19110]
424 Bourguignon LY,Wong G,Earle C,Chen L.Hyaluronan-CD44v3interaction with Oct4-Sox2-Nanog promotes mi R-302 expression leading to self-renewal,clonal formation,and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma.J Biol Chem 2012;287:32800-32824[PMID:22847005]
425 Liu F,Kong X,Lv L,Gao J.TGF-β1 acts through mi R-155 to down-regulate TP53INP1 in promoting epithelial-mesenchymal transition and cancer stem cell phenotypes.Cancer Lett 2015;359:288-298[PMID:25633840 DOI:10.1016/j.canlet.2015.01.030]
426 Ahmad A,Maitah MY,Ginnebaugh KR,Li Y,Bao B,Gadgeel SM,Sarkar FH.Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMTregulating mi RNAs.J Hematol Oncol 2013;6:77[PMID:24199791 DOI:10.1186/1756-8722-6-77]
427 Shen WW,Zeng Z,Zhu WX,Fu GH.Mi R-142-3p functions as a tumor suppressor by targeting CD133,ABCG2,and Lgr5 in colon cancer cells.J Mol Med(Berl)2013;91:989-1000[PMID:23619912 DOI:10.1007/s00109-013-1037-x]
428 Ji Q,Hao X,Zhang M,Tang W,Yang M,Li L,Xiang D,Desano JT,Bommer GT,Fan D,Fearon ER,Lawrence TS,Xu L.Micro RNA mi R-34 inhibits human pancreatic cancer tumorinitiating cells.PLo S One 2009;4:e6816[PMID:19714243 DOI:10 .1371/journal.pone.0006816]
429 Liu C,Kelnar K,Liu B,Chen X,Calhoun-Davis T,Li H,Patrawala L,Yan H,Jeter C,Honorio S,Wiggins JF,Bader AG,Fagin R,Brown D,Tang DG.The micro RNA mi R-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44.Nat Med 2011;17:211-215[PMID:21240262 DOI:10 .1038/nm.2284]
430 Garofalo M,Romano G,Di Leva G,Nuovo G,Jeon YJ,Ngankeu A,Sun J,Lovat F,Alder H,Condorelli G,Engelman JA,Ono M,Rho JK,Cascione L,Volinia S,Nephew KP,Croce CM.EGFR and MET receptor tyrosine kinase-altered micro RNA expression induces tumorigenesis and gefitinib resistance in lung cancers.Nat Med 2012;18:74-82[PMID:22157681 DOI:10.1038/nm.2577]
431 Garnier D,Magnus N,Meehan B,Kislinger T,Rak J.Qualitative changes in the proteome of extracellular vesicles accompanying cancer cell transition to mesenchymal state.Exp Cell Res2 0 1 3;319:2747-2757[PMID:23954818 DOI:10.1016/j.yexcr.2013.08.003]
432 Aga M,Bentz GL,Raffa S,Torrisi MR,Kondo S,Wakisaka N,Yoshizaki T,Pagano JS,Shackelford J.Exosomal HIF1αsupports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes.Oncogene 2014;33:4613-4622[PMID:24662828 DOI:10.1038/onc.2014.66]
433 Mu W,Rana S,Z?ller M.Host matrix modulation by tumor exosomes promotes motility and invasiveness.Neoplasia 2013;15:875-887[PMID:23908589]
434 Purushothaman A,Bandari SK,Liu J,Mobley JA,Brown EE,Sanderson RD.Fibronectin on the Surface of Myeloma Cellderived Exosomes Mediates Exosome-Cell Interactions.J Biol Chem 2016;291:1652-1663[PMID:26601950 DOI:10.1074/jbc.M115.686295]
435 Sung BH,Ketova T,Hoshino D,Zijlstra A,Weaver AM.Directional cell movement through tissues is controlled by exosome secretion.Nat Commun 2015;6:7164[PMID:25968605DOI:10.1038/ncomms8164]
436 Rieu S,Géminard C,Rabesandratana H,Sainte-Marie J,Vidal M.Exosomes released during reticulocyte maturation bind to fibronectin via integrin alpha4beta1.Eur J Biochem 2000;267:583-590[PMID:10632729]
437 Clayton A,Turkes A,Dewitt S,Steadman R,Mason MD,Hallett MB.Adhesion and signaling by B cell-derived exosomes:the role of integrins.FASEB J 2004;18:977-979[PMID:15059973]
438 Zech D,Rana S,Büchler MW,Z?ller M.Tumor-exosomes and leukocyte activation:an ambivalent crosstalk.Cell Commun Signal2012;10:37[PMID:23190502 DOI:10.1186/1478-811X-10-37]
439 Nolte-’t Hoen EN,Buschow SI,Anderton SM,Stoorvogel W,Wauben MH.Activated T cells recruit exosomes secreted by dendritic cells via LFA-1.Blood 2009;113:1977-1981[PMID:19064723 DOI:10.1182/blood-2008-08-174094]
440 Hoshino A,Costa-Silva B,Shen TL,Rodrigues G,Hashimoto A,Tesic Mark M,Molina H,Kohsaka S,Di Giannatale A,Ceder S,Singh S,Williams C,Soplop N,Uryu K,Pharmer L,King T,Bojmar L,Davies AE,Ararso Y,Zhang T,Zhang H,Hernandez J,Weiss JM,Dumont-Cole VD,Kramer K,Wexler LH,Narendran A,Schwartz GK,Healey JH,Sandstrom P,Labori KJ,Kure EH,Grandgenett PM,Hollingsworth MA,de Sousa M,Kaur S,Jain M,Mallya K,Batra SK,Jarnagin WR,Brady MS,Fodstad O,Muller V,Pantel K,Minn AJ,Bissell MJ,Garcia BA,Kang Y,Rajasekhar VK,Ghajar CM,Matei I,Peinado H,Bromberg J,Lyden D.Tumour exosome integrins determine organotropic metastasis.Nature 2015;527:329-335[PMID:26524530 DOI:10.1038/nature15756]
441 Rana S,Z?ller M.Exosome target cell selection and the importance of exosomal tetraspanins:a hypothesis.Biochem Soc Trans 2011;39:559-562[PMID:21428939 DOI:10.1042/BST0390559]
442 Van Gool SW,Vandenberghe P,de Boer M,Ceuppens JL.CD80,CD86 and CD40 provide accessory signals in a multiple-step T-cell activation model.Immunol Rev 1996;153:47-83[PMID:9010719]
443 Matzku S,Komitowski D,Mildenberger M,Z?ller M.Characterization of BSp73,a spontaneous rat tumor and its in vivo selected variants showing different metastasizing capacities.Invasion Metastasis 1983;3:109-123[PMID:6677621]
444 Tian T,Wang Y,Wang H,Zhu Z,Xiao Z.Visualizing of the cellular uptake and intracellular trafficking of exosomes by livecell microscopy.J Cell Biochem 2010;111:488-496[PMID:20533300 DOI:10.1002/jcb.22733]
445 Mulcahy LA,Pink RC,Carter DR.Routes and mechanisms of extracellular vesicle uptake.J Extracell Vesicles 2014;3:[PMID:25143819 DOI:10.3402/jev.v3.24641]
446 Taylor MJ,Lampe M,Merrifield CJ.A feedback loop between dynamin and actin recruitment during clathrin-mediated endocytosis.PLo S Biol 2012;10:e1001302[PMID:22505844DOI:10.1371/journal.pbio.1001302]
447 Parton RG,Simons K.The multiple faces of caveolae.Nat Rev Mol Cell Biol 2007;8:185-194[PMID:17318224]
448 Kerr MC,Teasdale RD.Defining macropinocytosis.Traffic 2009;10:364-371[PMID:19192253 DOI:10.1111/j.1600-0854.2009.00878.x]
449 Chernomordik LV,Kozlov MM.Mechanics of membrane fusion.Nat Struct Mol Biol 2008;15:675-683[PMID:18596814 DOI:10 .1038/nsmb.1455]
450 Ogorevc E,Kralj-Iglic V,Veranic P.The role of extracellular vesicles in phenotypic cancer transformation.Radiol Oncol 2013;47:197-205[PMID:24133383 DOI:10.2478/raon-2013-0037]
451 Belting M,Christianson HC.Role of exosomes and microvesicles in hypoxia-associated tumour development and cardiovascular disease.J Intern Med 2015;278:251-263[PMID:26153525 DOI:10 .1111/joim.12393]
452 Aharon A,Brenner B.Microparticles,thrombosis and cancer.Best Pract Res Clin Haematol 2009;22:61-69[PMID:19285273 DOI:10 .1016/j.beha.2008.11.002]
453 Rak J.Microparticles in cancer.Semin Thromb Hemost 2010;36:888-906[PMID:21049390 DOI:10.1055/s-0030-1267043]
454 Ratajczak MZ,Kucia M,Jadczyk T,Greco NJ,Wojakowski W,Tendera M,Ratajczak J.Pivotal role of paracrine effects in stem cell therapies in regenerative medicine:can we translate stem cellsecreted paracrine factors and microvesicles into better therapeutic strategies?Leukemia 2012;26:1166-1173[PMID:22182853 DOI:10 .1038/leu.2011.389]
455 Chiarini F,Lonetti A,Evangelisti C,Buontempo F,Orsini E,Evangelisti C,Cappellini A,Neri LM,Mc Cubrey JA,Martelli AM.Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment:From biology to therapeutic targeting.Biochim Biophys Acta 2016;1863:449-463[PMID:26334291DOI:10.1016/j.bbamcr.2015.08.015]
456 Filipazzi P,Bürdek M,Villa A,Rivoltini L,Huber V.Recent advances on the role of tumor exosomes in immunosuppression and disease progression.Semin Cancer Biol 2012;22:342-349[PMID:22369922 DOI:10.1016/j.semcancer.2012.02.005]
457 Kunigelis KE,Graner MW.The Dichotomy of Tumor Exosomes(TEX)in Cancer Immunity:Is It All in the Con TEXt?Vaccines(Basel)2015;3:1019-1051[PMID:26694473 DOI:10.3390/vaccines3041019]
458 Whiteside TL.Immune modulation of T-cell and NK(natural killer)cell activities by TEXs(tumour-derived exosomes).Biochem Soc Trans 2013;41:245-251[PMID:23356291 DOI:10 .1042/BST20120265]
459 Greening DW,Gopal SK,Xu R,Simpson RJ,Chen W.Exosomes and their roles in immune regulation and cancer.Semin Cell Dev Biol 2015;40:72-81[PMID:25724562 DOI:10.1016/j.semcdb.2015.02.009]
460 Bobrie A,Théry C.Exosomes and communication between tumours and the immune system:are all exosomes equal?Biochem Soc Trans 2013;41:263-267[PMID:23356294 DOI:10.1042/BST20120245]
461 Wieckowski E,Whiteside TL.Human tumor-derived vs dendritic cell-derived exosomes have distinct biologic roles and molecular profiles.Immunol Res 2006;36:247-254[PMID:17337785]
462 Taylor DD,Gercel-Taylor C.Exosomes/microvesicles:mediators of cancer-associated immunosuppressive microenvironments.Semin Immunopathol 2011;33:441-454[PMID:21688197 DOI:10 .1007/s00281-010-0234-8]
463 Gehrmann U,N?slund TI,Hiltbrunner S,Larssen P,Gabrielsson S.Harnessing the exosome-induced immune response for cancer immunotherapy.Semin Cancer Biol 2014;28:58-67[PMID:24859748 DOI:10.1016/j.semcancer.2014.05.003]
464 Claas C,Seiter S,Claas A,Savelyeva L,Schwab M,Z?ller M.Association between the rat homologue of CO-029,a metastasisassociated tetraspanin molecule and consumption coagulopathy.J Cell Biol 1998;141:267-280[PMID:9531564]
465 Ribeiro MF,Zhu H,Millard RW,Fan GC.Exosomes Function in Pro-and Anti-Angiogenesis.Curr Angiogenes 2013;2:54-59[PMID:25374792]
466 Finn NA,Searles CD.Intracellular and Extracellular mi RNAs in Regulation of Angiogenesis Signaling.Curr Angiogenes 2012;4:299-307[PMID:23914347]
467 Gai C,Carpanetto A,Deregibus MC,Camussi G.Extracellular vesicle-mediated modulation of angiogenesis.Histol Histopathol2016;31:379-391[PMID:26662176 DOI:10.14670/HH-11-708]
468 Janowska-Wieczorek A,Wysoczynski M,Kijowski J,MarquezCurtis L,Machalinski B,Ratajczak J,Ratajczak MZ.Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer.Int J Cancer 2005;113:752-760[PMID:15499615]
469 Shimoda M,Khokha R.Proteolytic factors in exosomes.Proteomics 2013;13:1624-1636[PMID:23526769 DOI:10.1002/pmic.201200458]
470 Sevenich L,Joyce JA.Pericellular proteolysis in cancer.Genes Dev2014;28:2331-2347[PMID:25367033 DOI:10.1101/gad.250647.114]
471 Stoeck A,Keller S,Riedle S,Sanderson MP,Runz S,Le Naour F,Gutwein P,Ludwig A,Rubinstein E,Altevogt P.A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44.Biochem J 2006;393:609-618[PMID:16229685]
472 Nakamura H,Suenaga N,Taniwaki K,Matsuki H,Yonezawa K,Fujii M,Okada Y,Seiki M.Constitutive and induced CD44shedding by ADAM-like proteases and membrane-type 1 matrix metalloproteinase.Cancer Res 2004;64:876-882[PMID:14871815]
473 Chetty C,Vanamala SK,Gondi CS,Dinh DH,Gujrati M,Rao JS.MMP-9 induces CD44 cleavage and CD44 mediated cell migration in glioblastoma xenograft cells.Cell Signal 2012;24:549-559[PMID:22024282 DOI:10.1016/j.cellsig.2011.10.008]
474 Tsaktanis T,Kremling H,Pav?i?M,von Stackelberg R,Mack B,Fukumori A,Steiner H,Vielmuth F,Spindler V,Huang Z,Jakubowski J,Stoecklein NH,Luxenburger E,Lauber K,Lenar?i?B,Gires O.Cleavage and cell adhesion properties of human epithelial cell adhesion molecule(HEPCAM).J Biol Chem2015;290:24574-24591[PMID:26292218 DOI:10.1074/jbc.M115.662700]
475 Lokeshwar VB,Mirza S,Jordan A.Targeting hyaluronic acid family for cancer chemoprevention and therapy.Adv Cancer Res2014;123:35-65[PMID:25081525 DOI:10.1016/B978-0-12-800092-2.00002-2]
476 Rilla K,Siiskonen H,Tammi M,Tammi R.Hyaluronan-coated extracellular vesicles--a novel link between hyaluronan and cancer.Adv Cancer Res 2014;123:121-148[PMID:25081528 DOI:10 .1016/B978-0-12-800092-2.00005-8]
477 Seiki M.Membrane-type 1 matrix metalloproteinase:a key enzyme for tumor invasion.Cancer Lett 2003;194:1-11[PMID:12706853]
478 Bauvois B.New facets of matrix metalloproteinases MMP-2and MMP-9 as cell surface transducers:outside-in signaling and relationship to tumor progression.Biochim Biophys Acta 2012;1825:29-36[PMID:22020293 DOI:10.1016/j.bbcan.2011.10.001]
479 Ramteke A,Ting H,Agarwal C,Mateen S,Somasagara R,Hussain A,Graner M,Frederick B,Agarwal R,Deep G.Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules.Mol Carcinog 2015;54:554-565[PMID:24347249 DOI:10.1002/mc.22124]
480 Tauro BJ,Mathias RA,Greening DW,Gopal SK,Ji H,Kapp EA,Coleman BM,Hill AF,Kusebauch U,Hallows JL,Shteynberg D,Moritz RL,Zhu HJ,Simpson RJ.Oncogenic H-ras reprograms Madin-Darby canine kidney(MDCK)cell-derived exosomal proteins following epithelial-mesenchymal transition.Mol Cell Proteomics 2013;12:2148-2159[PMID:23645497 DOI:10.1074/mcp.M112.027086]
481 Mazurov D,Barbashova L,Filatov A.Tetraspanin protein CD9interacts with metalloprotease CD10 and enhances its release via exosomes.FEBS J 2013;280:1200-1213[PMID:23289620 DOI:10 .1111/febs.12110]
482 Liu T,Mendes DE,Berkman CE.Functional prostate-specific membrane antigen is enriched in exosomes from prostate cancer cells.Int J Oncol 2014;44:918-922[PMID:24424840 DOI:10 .3892/ijo.2014.2256]
483 Hakulinen J,Sankkila L,Sugiyama N,Lehti K,Keski-Oja J.Secretion of active membrane type 1 matrix metalloproteinase(MMP-14)into extracellular space in microvesicular exosomes.J Cell Biochem 2008;105:1211-1218[PMID:18802920 DOI:10 .1002/jcb.21923]
484 Hendrix A,Westbroek W,Bracke M,De Wever O.An ex(o)citing machinery for invasive tumor growth.Cancer Res 2010;70:9533-9537[PMID:21098711 DOI:10.1158/0008-5472.CAN-10-3248]
485 Hood JL,San RS,Wickline SA.Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis.Cancer Res2011;71:3792-3801[PMID:21478294 DOI:10.1158/0008-5472.CAN-10-4455]
486 Peinado H,Ale?kovi?M,Lavotshkin S,Matei I,Costa-Silva B,Moreno-Bueno G,Hergueta-Redondo M,Williams C,GarcíaSantos G,Ghajar C,Nitadori-Hoshino A,Hoffman C,Badal K,Garcia BA,Callahan MK,Yuan J,Martins VR,Skog J,Kaplan RN,Brady MS,Wolchok JD,Chapman PB,Kang Y,Bromberg J,Lyden D.Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.Nat Med2012;18:883-891[PMID:22635005 DOI:10.1038/nm.2753]
487 Webber J,Yeung V,Clayton A.Extracellular vesicles as modulators of the cancer microenvironment.Semin Cell Dev Biol 2015;40:27-34[PMID:25662446 DOI:10.1016/j.semcdb.2015.01.013]
488 Altevogt P,Bretz NP,Ridinger J,Utikal J,Umansky V.Novel insights into exosome-induced,tumor-associated inflammation and immunomodulation.Semin Cancer Biol 2014;28:51-57[PMID:24769223 DOI:10.1016/j.semcancer.2014.04.008]
489 Whitehead B,Wu L,Hvam ML,Aslan H,Dong M,Dyrskj?t L,Ostenfeld MS,Moghimi SM,Howard KA.Tumour exosomes display differential mechanical and complement activation properties dependent on malignant state:implications in endothelial leakiness.J Extracell Vesicles 2015;4:29685[PMID:26714455DOI:10.3402/jev.v4.29685]
490 Fontana S,Saieva L,Taverna S,Alessandro R.Contribution of proteomics to understanding the role of tumor-derived exosomes in cancer progression:state of the art and new perspectives.Proteomics 2013;13:1581-1594[PMID:23401131 DOI:10.1002/pmic.201200398]
491 Brandt DT,Xu J,Steinbeisser H,Grosse R.Regulation of myocardin-related transcriptional coactivators through cofactor interactions in differentiation and cancer.Cell Cycle 2009;8:2523-2527[PMID:19625774]
492 Lee NP,Poon RT,Shek FH,Ng IO,Luk JM.Role of cadherin-17 in oncogenesis and potential therapeutic implications in hepatocellular carcinoma.Biochim Biophys Acta 2010;1806:138-145[PMID:20580775 DOI:10.1016/j.bbcan.2010.05.002]
493 Mathew SJ,Haubert D,Kr?nke M,Leptin M.Looking beyond death:a morphogenetic role for the TNF signalling pathway.J Cell Sci 2009;122:1939-1946[PMID:19494121 DOI:10.1242/jcs.044487]
494 Liu QS,Zhang J,Liu M,Dong WG.Lentiviral-mediated mi RNA against liver-intestine cadherin suppresses tumor growth and invasiveness of human gastric cancer.Cancer Sci 2010;101:1807-1812[PMID:20500517 DOI:10.1111/j.1349-7006.2010.01600.x]
495 Pang W,Su J,Wang Y,Feng H,Dai X,Yuan Y,Chen X,Yao W.Pancreatic cancer-secreted mi R-155 implicates in the conversion from normal fibroblasts to cancer-associated fibroblasts.Cancer Sci2015;106:1362-1369[PMID:26195069 DOI:10.1111/cas.12747]
496 Ratajczak J,Miekus K,Kucia M,Zhang J,Reca R,Dvorak P,Ratajczak MZ.Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors:evidence for horizontal transfer of m RNA and protein delivery.Leukemia 2006;20:847-856[PMID:16453000]
497 Pan Q,Ramakrishnaiah V,Henry S,Fouraschen S,de Ruiter PE,Kwekkeboom J,Tilanus HW,Janssen HL,van der Laan LJ.Hepatic cell-to-cell transmission of small silencing RNA can extend the therapeutic reach of RNA interference(RNAi).Gut 2012;61:1330-1339[PMID:22198713 DOI:10.1136/gutjnl-2011-300449]
498 Verweij FJ,Middeldorp JM,Pegtel DM.Intracellular signaling controlled by the endosomal-exosomal pathway.Commun Integr Biol 2012;5:88-93[PMID:22482020]
499 Higginbotham JN,Demory Beckler M,Gephart JD,Franklin JL,Bogatcheva G,Kremers GJ,Piston DW,Ayers GD,Mc Connell RE,Tyska MJ,Coffey RJ.Amphiregulin exosomes increase cancer cell invasion.Curr Biol 2011;21:779-786[PMID:21514161 DOI:10 .1016/j.cub.2011.03.043]
500 Yang M,Chen J,Su F,Yu B,Su F,Lin L,Liu Y,Huang JD,Song E.Microvesicles secreted by macrophages shuttle invasionpotentiating micro RNAs into breast cancer cells.Mol Cancer 2011;10:117[PMID:21939504 DOI:10.1186/1476-4598-10-117]
501 Zhang Y,Liu D,Chen X,Li J,Li L,Bian Z,Sun F,Lu J,Yin Y,Cai X,Sun Q,Wang K,Ba Y,Wang Q,Wang D,Yang J,Liu P,Xu T,Yan Q,Zhang J,Zen K,Zhang CY.Secreted monocytic mi R-150enhances targeted endothelial cell migration.Mol Cell 2010;39:133-144[PMID:20603081 DOI:10.1016/j.molcel.2010.06.010]
502 Roninson IB.Molecular mechanism of multidrug resistance in tumor cells.Clin Physiol Biochem 1987;5:140-151[PMID:2887329]
503 Bebawy M,Combes V,Lee E,Jaiswal R,Gong J,Bonhoure A,Grau GE.Membrane microparticles mediate transfer of P-glycoprotein to drug sensitive cancer cells.Leukemia 2009;23:1643-1649[PMID:19369960 DOI:10.1038/leu.2009.76]
504 Aga M,Bradley JM,Wanchu R,Yang YF,Acott TS,Keller KE.Differential effects of caveolin-1 and-2 knockdown on aqueous outflow and altered extracellular matrix turnover in caveolin-silenced trabecular meshwork cells.Invest Ophthalmol Vis Sci 2014;55:5497-5509[PMID:25103269 DOI:10.1167/iovs.14-14519]