Common stemness regulators of embryonic and cancer stem cells
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摘要
Pluripotency of embryonic stem cells(ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal trans-ducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors(cancer stem cells), provides a common conceptual and research frame-work for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.
Pluripotency of embryonic stem cells(ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal trans-ducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors(cancer stem cells), provides a common conceptual and research frame-work for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.
Pluripotency of embryonic stem cells(ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal trans-ducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors(cancer stem cells), provides a common conceptual and research frame-work for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.
引文
1 Evans MJ,Kaufman MH.Establishment in culture of pluripotential cells from mouse embryos.Nature 1981;292:154-156[PMID:7242681]
2 Thomson JA,Itskovitz-Eldor J,Shapiro SS,Waknitz MA,Swiergiel JJ,Marshall VS,Jones JM.Embryonic stem cell lines derived from human blastocysts.Science 1998;282:1145-1147[PMID:9804556]
3 Tesar PJ,Chenoweth JG,Brook FA,Davies TJ,Evans EP,Mack DL,Gardner RL,McK ay RD.New cell lines from mouse epiblast share defining features with human embryonic stem cells.Nature2007;448:196-199[PMID:17597760]
4 Boyer LA,Lee TI,Cole MF,Johnstone SE,Levine SS,Zucker JP,Guenther MG,Kumar RM,Murray HL,Jenner RG,Gifford DK,Melton DA,Jaenisch R,Young RA.Core transcriptional regulatory circuitry in human embryonic stem cells.Cell 2005;122:947-956[PMID:16153702 DOI:10.1016/j.cell.2005.08.020]
5 Theunissen TW,Jaenisch R.Molecular control of induced pluripotency.Cell Stem Cell 2014;14:720-734[PMID:24905163DOI:10.1016/j.stem.2014.05.002]
6 Cherry AB,Daley GQ.Reprogrammed cells for disease modeling and regenerative medicine.Annu Rev Med 2013;64:277-290[PMID:23327523 DOI:10.1146/annurev-med-050311-163324]
7 Solter D.From teratocarcinomas to embryonic stem cells and beyond:a history of embryonic stem cell research.Nat Rev Genet2006;7:319-327[PMID:16534514 DOI:10.1038/nrg1827]
8 Friedmann-Morvinski D,Verma IM.Dedifferentiation and reprogramming:origins of cancer stem cells.EMBO Rep 2014;15:244 -253[PMID:24531722 DOI:10.1002/embr.201338254]
9 Goding CR,Pei D,Lu X.Cancer:pathological nuclear reprog-ramming?Nat Rev Cancer 2014;14:568-573[PMID:25030952 DOI:10 .1038/nrc3781]
10 Kreso A,Dick JE.Evolution of the cancer stem cell model.Cell Stem Cell 2014;14:275-291[PMID:24607403 DOI:10.1016/j.stem.2014.02.006]
11 Lobo NA,Shimono Y,Qian D,Clarke MF.The biology of cancer stem cells.Annu Rev Cell Dev Biol 2007;23:675-699[PMID:17645413]
12 O’Connor ML,Xiang D,Shigdar S,Macdonald J,Li Y,Wang T,Pu C,Wang Z,Qiao L,Duan W.Cancer stem cells:A contentious hypothesis now moving forward.Cancer Lett 2014;344:180-187[PMID:24333726 DOI:10.1016/j.canlet.2013.11.012]
13 Pattabiraman DR,Weinberg RA.Tackling the cancer stem cells-what challenges do they pose?Nat Rev Drug Discov 2014;13:497 -512[PMID:24981363 DOI:10.1038/nrd4253]
14 Li R,Liang J,Ni S,Zhou T,Qing X,Li H,He W,Chen J,Li F,Zhuang Q,Qin B,Xu J,Li W,Yang J,Gan Y,Qin D,Feng S,Song H,Yang D,Zhang B,Zeng L,Lai L,Esteban MA,Pei D.A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts.Cell Stem Cell 2010;7:51 -63[PMID:20621050 DOI:10.1016/j.stem.2010.04.014]
15 Ben-Porath I,Thomson MW,Carey VJ,Ge R,Bell GW,Regev A,Weinberg RA.An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors.Nat Genet 2008;40:499-507[PMID:18443585 DOI:10.1038/ng.127]
16 Wong DJ,Liu H,Ridky TW,Cassarino D,Segal E,Chang HY.Module map of stem cell genes guides creation of epithelial cancer stem cells.Cell Stem Cell 2008;2:333-344[PMID:18397753 DOI:10 .1016/j.stem.2008.02.009]
17 Zhao W,Ji X,Zhang F,Li L,Ma L.Embryonic stem cell markers.Molecules 2012;17:6196-6236[PMID:22634835 DOI:10.3390/molecules17066196]
18 Knowles BB,Aden DP,Solter D.Monoclonal antibody detecting a stage-specific embryonic antigen(SSEA-1)on preimplantation mouse embryos and teratocarcinoma cells.Curr Top Microbiol Immunol 1978;81:51-53[PMID:688761]
19 Solter D,Knowles BB.Monoclonal antibody defining a stage-specific mouse embryonic antigen(SSEA-1).Proc Natl Acad Sci USA 1978;75:5565-5569[PMID:281705]
20 Henderson JK,Draper JS,Baillie HS,Fishel S,Thomson JA,Moore H,Andrews PW.Preimplantation human embryos and embryonic stem cells show comparable expression of stage-specific embryonic antigens.Stem Cells 2002;20:329-337[PMID:12110702 DOI:10.1634/stemcells.20-4-329]
21 Kannagi R,Levery SB,Ishigami F,Hakomori S,Shevinsky LH,Knowles BB,Solter D.New globoseries glycosphingolipids in human teratocarcinoma reactive with the monoclonal antibody directed to a developmentally regulated antigen,stage-specific embryonic antigen 3.J Biol Chem 1983;258:8934-8942[PMID:6863318]
22 Shevinsky LH,Knowles BB,Damjanov I,Solter D.Monoclonal antibody to murine embryos defines a stage-specific embryonic antigen expressed on mouse embryos and human teratocarcinoma cells.Cell 1982;30:697-705[PMID:6183004]
23 Giwercman A,Andrews PW,J?rgensen N,Müller J,Graem N,Skakkebaek NE.Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis.Cancer 1993;72:1308-1314[PMID:8339218]
24 Schopperle WM,De Wolf WC.The TRA-1-60 and TRA-1-81human pluripotent stem cell markers are expressed on podocalyxin in embryonal carcinoma.Stem Cells 2007;25:723-730[PMID:17124010]
25 Tanabe K,Nakamura M,Narita M,Takahashi K,Yamanaka S.Maturation,not initiation,is the major roadblock during reprogramming toward pluripotency from human fibroblasts.Proc Natl Acad Sci USA 2013;110:12172-12179[PMID:23812749DOI:10.1073/pnas.1310291110]
26 Sundberg M,Jansson L,Ketolainen J,Pihlajam?ki H,Suuronen R,Skottman H,Inzunza J,Hovatta O,Narkilahti S.CD marker expression profiles of human embryonic stem cells and their neural derivatives,determined using flow-cytometric analysis,reveal a novel CD marker for exclusion of pluripotent stem cells.Stem Cell Res 2009;2:113-124[PMID:19383417 DOI:10.1016/j.scr.2008.08.001]
27 Evseenko D,Zhu Y,Schenke-Layland K,Kuo J,Latour B,Ge S,Scholes J,Dravid G,Li X,MacL ellan WR,Crooks GM.Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells.Proc Natl Acad Sci USA 2010;107:13742-13747[PMID:20643952 DOI:10.1073/pnas.1002077107]
28 Klauzinska M,Castro NP,Rangel MC,Spike BT,Gray PC,Bertolette D,Cuttitta F,Salomon D.The multifaceted role of the embryonic gene Cripto-1 in cancer,stem cells and epithelial-mesenchymal transition.Semin Cancer Biol 2014;29:51-58[PMID:25153355 DOI:10.1016/j.semcancer.2014.08.003]
29 Parish CL,Parisi S,Persico MG,Arenas E,Minchiotti G.Cripto as a target for improving embryonic stem cell-based therapy in Parkinson’s disease.Stem Cells 2005;23:471-476[PMID:15790767]
30 Al-Hajj M,Wicha MS,Benito-Hernandez A,Morrison SJ,Clarke MF.Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci USA 2003;100:3983-3988[PMID:12629218DOI:10.1073/pnas.0530291100]
31 Kim MP,Fleming JB,Wang H,Abbruzzese JL,Choi W,Kopetz S,McC onkey DJ,Evans DB,Gallick GE.ALDH activity selectively defines an enhanced tumor-initiating cell population relative to CD133 expression in human pancreatic adenocarcinoma.PLo S One 2011;6:e20636[PMID:21695188 DOI:10.1371/journal.pone.0020636]
32 Afify A,Purnell P,Nguyen L.Role of CD44s and CD44v6 on human breast cancer cell adhesion,migration,and invasion.Exp Mol Pathol 2009;86:95-100[PMID:19167378 DOI:10.1016/j.yexmp.2008.12.003]
33 Bourguignon LY,Spevak CC,Wong G,Xia W,Gilad E.Hyaluro-nan-CD44 interaction with protein kinase C(epsilon)promotes oncogenic signaling by the stem cell marker Nanog and the Production of micro RNA-21,leading to down-regulation of the tumor suppressor protein PDCD4,anti-apoptosis,and chemotherapy resistance in breast tumor cells.J Biol Chem 2009;284:26533-26546[PMID:19633292 DOI:10.1074/jbc.M109.027466]
34 Schabath H,Runz S,Joumaa S,Altevogt P.CD24 affects CXCR4function in pre-B lymphocytes and breast carcinoma cells.J Cell Sci 2006;119:314-325[PMID:16390867]
35 Allan AL.Cancer stem cells in solid tumors.New York:Humana Press,2011
36 Huang EH,Hynes MJ,Zhang T,Ginestier C,Dontu G,Appelman H,Fields JZ,Wicha MS,Boman BM.Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells(SC)and tracks SC overpopulation during colon tumorigenesis.Cancer Res 2009;69:3382-3389[PMID:19336570 DOI:10 .1158/0008-5472.CAN-08-4418]
37 Moreb JS.Aldehyde dehydrogenase as a marker for stem cells.Curr Stem Cell Res Ther 2008;3:237-246[PMID:19075754]
38 Singh SK,Clarke ID,Terasaki M,Bonn VE,Hawkins C,Squire J,Dirks PB.Identification of a cancer stem cell in human brain tumors.Cancer Res 2003;63:5821-5828[PMID:14522905]
39 Irollo E,Pirozzi G.CD133:to be or not to be,is this the real question?Am J Transl Res 2013;5:563-581[PMID:24093054]
40 Salnikov AV,Gladkich J,Moldenhauer G,Volm M,Mattern J,Herr I.CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients.Int J Cancer 2010;126:950-958[PMID:19676044DOI:10.1002/ijc.24822]
41 Beier D,Hau P,Proescholdt M,Lohmeier A,Wischhusen J,Oefner PJ,Aigner L,Brawanski A,Bogdahn U,Beier CP.CD133(+)and CD133(-)glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles.Cancer Res 2007;67:4010-4015[PMID:17483311]
42 Hemmati HD,Nakano I,Lazareff JA,Masterman-Smith M,Geschwind DH,Bronner-Fraser M,Kornblum HI.Cancerous stem cells can arise from pediatric brain tumors.Proc Natl Acad Sci USA 2003;100:15178-15183[PMID:14645703 DOI:10.1073/pnas.2036535100]
43 Zinzi L,Capparelli E,Cantore M,Contino M,Leopoldo M,Colabufo NA.Small and Innovative Molecules as New Strategy to Revert MDR.Front Oncol 2014;4:2[PMID:24478983 DOI:10 .3389/fonc.2014.00002]
44 Choi YH,Yu AM.ABC transporters in multidrug resistance and pharmacokinetics,and strategies for drug development.Curr Pharm Des 2014;20:793-807[PMID:23688078]
45 Read TA,Fogarty MP,Markant SL,McL endon RE,Wei Z,Ellison DW,Febbo PG,Wechsler-Reya RJ.Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma.Cancer Cell 2009;15:135-147[PMID:19185848 DOI:10.1016/j.ccr.2008.12.016]
46 Gao MQ,Choi YP,Kang S,Youn JH,Cho NH.CD24+cells from hierarchically organized ovarian cancer are enriched in cancer stem cells.Oncogene 2010;29:2672-2680[PMID:20190812 DOI:10 .1038/onc.2010.35]
47 Ishiwata T,Teduka K,Yamamoto T,Kawahara K,Matsuda Y,Naito Z.Neuroepithelial stem cell marker nestin regulates the migration,invasion and growth of human gliomas.Oncol Rep 2011;26 :91-99[PMID:21503585 DOI:10.3892/or.2011.1267]
48 Nakai E,Park K,Yawata T,Chihara T,Kumazawa A,Nakabayashi H,Shimizu K.Enhanced MDR1 expression and chemoresistance of cancer stem cells derived from glioblastoma.Cancer Invest 2009;27:901 -908[PMID:19832037 DOI:10.3109/07357900801946679]
49 Ricci-Vitiani L,Lombardi DG,Pilozzi E,Biffoni M,Todaro M,Peschle C,De Maria R.Identification and expansion of human colon-cancer-initiating cells.Nature 2007;445:111-115[PMID:17122771]
50 Trzpis M,McL aughlin PM,de Leij LM,Harmsen MC.Epithelial cell adhesion molecule:more than a carcinoma marker and adhesion molecule.Am J Pathol 2007;171:386-395[PMID:17600130 DOI:10 .2353/ajpath.2007.070152]
51 Dalerba P,Dylla SJ,Park IK,Liu R,Wang X,Cho RW,Hoey T,Gurney A,Huang EH,Simeone DM,Shelton AA,Parmiani G,Castelli C,Clarke MF.Phenotypic characterization of human colorectal cancer stem cells.Proc Natl Acad Sci USA 2007;104:10158-10163[PMID:17548814 DOI:10.1073/pnas.0703478104]
52 Weidle UH,Eggle D,Klostermann S,Swart GW.ALCAM/CD166:cancer-related issues.Cancer Genomics Proteomics 2010;7:231 -243[PMID:20952758]
53 Brizzi MF,Tarone G,Defilippi P.Extracellular matrix,integrins,and growth factors as tailors of the stem cell niche.Curr Opin Cell Biol 2012;24:645-651[PMID:22898530 DOI:10.1016/j.ceb.2012.07.001]
54 Wu XS,Xi HQ,Chen L.Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival.World J Surg Oncol 2012;10:244[PMID:23153436 DOI:10.1186/1477-7819 -10-244]
55 de Lau WB,Snel B,Clevers HC.The R-spondin protein family.Genome Biol 2012;13:242[PMID:22439850 DOI:10.1186/gb-2012-13-3-242]
56 Takahashi H,Ishii H,Nishida N,Takemasa I,Mizushima T,Ikeda M,Yokobori T,Mimori K,Yamamoto H,Sekimoto M,Doki Y,Mori M.Significance of Lgr5(+ve)cancer stem cells in the colon and rectum.Ann Surg Oncol 2011;18:1166-1174[PMID:21125339 DOI:10.1245/s10434-010-1373-9]
57 Li C,Heidt DG,Dalerba P,Burant CF,Zhang L,Adsay V,Wicha M,Clarke MF,Simeone DM.Identification of pancreatic cancer stem cells.Cancer Res 2007;67:1030-1037[PMID:17283135]
58 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]
59 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]
60 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]
61 Sharpe B,Beresford M,Bowen R,Mitchard J,Chalmers AD.Searching for prostate cancer stem cells:markers and methods.Stem Cell Rev 2013;9:721-730[PMID:23775699 DOI:10.1007/s12015-013-9453-4]
62 Tomao F,Papa A,Strudel M,Rossi L,Lo Russo G,Benedetti Panici P,Ciabatta FR,Tomao S.Investigating molecular profiles of ovarian cancer:an update on cancer stem cells.J Cancer 2014;5:301 -310[PMID:24723972 DOI:10.7150/jca.8610]
63 Luo L,Zeng J,Liang B,Zhao Z,Sun L,Cao D,Yang J,Shen K.Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome.Exp Mol Pathol 2011;91:596 -602[PMID:21787767 DOI:10.1016/j.yexmp.2011.06.005]
64 La Porta CA,Zapperi S.Human breast and melanoma cancer stem cells biomarkers.Cancer Lett 2013;338:69-73[PMID:22445909DOI:10.1016/j.canlet.2012.03.017]
65 Monzani E,Facchetti F,Galmozzi E,Corsini E,Benetti A,Cavazzin C,Gritti A,Piccinini A,Porro D,Santinami M,Invernici G,Parati E,Alessandri G,La Porta CA.Melanoma contains CD133and ABCG2 positive cells with enhanced tumourigenic potential.Eur J Cancer 2007;43:935-946[PMID:17320377]
66 Redmer T,Welte Y,Behrens D,Fichtner I,Przybilla D,Wruck W,Yaspo ML,Lehrach H,Sch?fer R,Regenbrecht CR.The nerve growth factor receptor CD271 is crucial to maintain tumorigenicity and stem-like properties of melanoma cells.PLo S One 2014;9:e92596[PMID:24799129 DOI:10.1371/journal.pone.0092596]
67 Taghizadeh R,Noh M,Huh YH,Ciusani E,Sigalotti L,Maio M,Arosio B,Nicotra MR,Natali P,Sherley JL,La Porta CA.CXCR6,a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal,identifies more aggressive human melanoma cancer stem cells.PLo S One 2010;5:e15183[PMID:21203549 DOI:10 .1371/journal.pone.0015183]
68 Kumar SM,Liu S,Lu H,Zhang H,Zhang PJ,Gimotty PA,Guerra M,Guo W,Xu X.Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation.Oncogene 2012;31:4898-4911[PMID:22286766 DOI:10.1038/onc.2011.656]
69 Eramo A,Lotti F,Sette G,Pilozzi E,Biffoni M,Di Virgilio A,Conticello C,Ruco L,Peschle C,De Maria R.Identification and expansion of the tumorigenic lung cancer stem cell population.Cell Death Differ 2008;15:504-514[PMID:18049477]
70 Chen YC,Hsu HS,Chen YW,Tsai TH,How CK,Wang CY,Hung SC,Chang YL,Tsai ML,Lee YY,Ku HH,Chiou SH.Oct4expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells.PLo S One 2008;3:e2637[PMID:18612434 DOI:10.1371/journal.pone.0002637]
71 Kimura M,Takenobu H,Akita N,Nakazawa A,Ochiai H,Shimozato O,Fujimura Y,Koseki H,Yoshino I,Kimura H,Nakagawara A,Kamijo T.Bmi1 regulates cell fate via tumor suppressor WWOX repression in small-cell lung cancer cells.Cancer Sci 2011;102:983-990[PMID:21276135 DOI:10.1111/j.1349-7006.2011.01891.x]
72 Yin S,Li J,Hu C,Chen X,Yao M,Yan M,Jiang G,Ge C,Xie H,Wan D,Yang S,Zheng S,Gu J.CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity.Int J Cancer 2007;120:1444-1450[PMID:17205516]
73 Mishra L,Banker T,Murray J,Byers S,Thenappan A,He AR,Shetty K,Johnson L,Reddy EP.Liver stem cells and hepatocellular carcinoma.Hepatology 2009;49:318-329[PMID:19111019 DOI:10 .1002/hep.22704]
74 Ji J,Wang XW.Clinical implications of cancer stem cell biology in hepatocellular carcinoma.Semin Oncol 2012;39:461-472[PMID:22846863 DOI:10.1053/j.seminoncol.2012.05.011]
75 Prince ME,Sivanandan R,Kaczorowski A,Wolf GT,Kaplan MJ,Dalerba P,Weissman IL,Clarke MF,Ailles LE.Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma.Proc Natl Acad Sci USA 2007;104:973 -978[PMID:17210912]
76 Okamoto A,Chikamatsu K,Sakakura K,Hatsushika K,Takahashi G,Masuyama K.Expansion and characterization of cancer stem- like cells in squamous cell carcinoma of the head and neck.Oral Oncol 2009;45:633-639[PMID:19027347 DOI:10.1016/j.oralon cology.2008.10.003]
77 Major AG,Pitty LP,Farah CS.Cancer stem cell markers in head and neck squamous cell carcinoma.Stem Cells Int 2013;2013:319489[PMID:23533441 DOI:10.1155/2013/319489]
78 Dreesen O,Brivanlou AH.Signaling pathways in cancer and embryonic stem cells.Stem Cell Rev 2007;3:7-17[PMID:17873377]
79 Takebe N,Harris PJ,Warren RQ,Ivy SP.Targeting cancer stem cells by inhibiting Wnt,Notch,and Hedgehog pathways.Nat Rev Clin Oncol 2011;8:97-106[PMID:21151206 DOI:10.1038/nrclinonc.2010.196]
80 Karamboulas C,Ailles L.Developmental signaling pathways in cancer stem cells of solid tumors.Biochim Biophys Acta 2013;1830:2481-2495[PMID:23196196 DOI:10.1016/j.bbagen.2012.11.008]
81 Niwa H,Burdon T,Chambers I,Smith A.Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3.Genes Dev 1998;12:2048-2060[PMID:9649508]
82 Frank DA.STAT3 as a central mediator of neoplastic cellular transformation.Cancer Lett 2007;251:199-210[PMID:17129668DOI:10.1016/j.canlet.2006.10.017]
83 Lin L,Liu A,Peng Z,Lin HJ,Li PK,Li C,Lin J.STAT3 is necessary for proliferation and survival in colon cancer-initiating cells.Cancer Res 2011;71:7226-7237[PMID:21900397 DOI:10 .1158/0008-5472.CAN-10-4660]
84 Kroon P,Berry PA,Stower MJ,Rodrigues G,Mann VM,Simms M,Bhasin D,Chettiar S,Li C,Li PK,Maitland NJ,Collins AT.JAK-STAT blockade inhibits tumor initiation and clonogenic recovery of prostate cancer stem-like cells.Cancer Res 2013;73:5288-5298[PMID:23824741 DOI:10.1158/0008-5472.CAN-13-0874]
85 Marotta LL,Almendro V,Marusyk A,Shipitsin M,Schemme J,Walker SR,Bloushtain-Qimron N,Kim JJ,Choudhury SA,Maruyama R,Wu Z,G?nen M,Mulvey LA,Bessarabova MO,Huh SJ,Silver SJ,Kim SY,Park SY,Lee HE,Anderson KS,Richardson AL,Nikolskaya T,Nikolsky Y,Liu XS,Root DE,Hahn WC,Frank DA,Polyak K.The JAK2/STAT3 signaling pathway is required for growth of CD44?CD24?stem cell-like breast cancer cells in human tumors.J Clin Invest 2011;121:2723-2735[PMID:21633165 DOI:10 .1172/JCI44745]
86 Logan CY,Nusse R.The Wnt signaling pathway in development and disease.Annu Rev Cell Dev Biol 2004;20:781-810[PMID:15473860 DOI:10.1146/annurev.cellbio.20.010403.113126]
87 Li VS,Ng SS,Boersema PJ,Low TY,Karthaus WR,Gerlach JP,Mohammed S,Heck AJ,Maurice MM,Mahmoudi T,Clevers H.Wnt signaling through inhibition ofβ-catenin degradation in an intact Axin1 complex.Cell 2012;149:1245-1256[PMID:22682247 DOI:10.1016/j.cell.2012.05.002]
88 He TC,Sparks AB,Rago C,Hermeking H,Zawel L,da Costa LT,Morin PJ,Vogelstein B,Kinzler KW.Identification of c-MYC as a target of the APC pathway.Science 1998;281:1509-1512[PMID:9727977]
89 Tetsu O,McC ormick F.Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.Nature 1999;398:422-426[PMID:10201372 DOI:10.1038/18884]
90 ten Berge D,Kurek D,Blauwkamp T,Koole W,Maas A,Eroglu E,Siu RK,Nusse R.Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells.Nat Cell Biol 2011;13:1070-1075[PMID:21841791 DOI:10.1038/ncb2314]
91 Sato N,Meijer L,Skaltsounis L,Greengard P,Brivanlou AH.Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor.Nat Med 2004;10:55-63[PMID:14702635 DOI:10.1038/nm979]
92 Wray J,Kalkan T,Gomez-Lopez S,Eckardt D,Cook A,Kemler R,Smith A.Inhibition of glycogen synthase kinase-3 alleviates Tcf3repression of the pluripotency network and increases embryonic stem cell resistance to differentiation.Nat Cell Biol 2011;13:838 -845[PMID:21685889 DOI:10.1038/ncb2267]
93 Valenta T,Gay M,Steiner S,Draganova K,Zemke M,Hoffmans R,Cinelli P,Aguet M,Sommer L,Basler K.Probing transcription-specific outputs ofβ-catenin in vivo.Genes Dev 2011;25:2631-2643[PMID:22190459 DOI:10.1101/gad.181289.111]
94 Holland JD,Klaus A,Garratt AN,Birchmeier W.Wnt signaling in stem and cancer stem cells.Curr Opin Cell Biol 2013;25:254-264[PMID:23347562 DOI:10.1016/j.ceb.2013.01.004]
95 Niwa H.Wnt:what’s needed to maintain pluripotency?Nat Cell Biol 2011;13:1024-1026[PMID:21892143 DOI:10.1038/ncb2333]
96 Kelly KF,Ng DY,Jayakumaran G,Wood GA,Koide H,Doble BW.β-catenin enhances Oct4 activity and reinforces pluripotency through a TCF-independent mechanism.Cell Stem Cell 2011;8:214 -227[PMID:21295277 DOI:10.1016/j.stem.2010.12.010]
97 Davidson KC,Adams AM,Goodson JM,Mc Donald CE,Potter JC,Berndt JD,Biechele TL,Taylor RJ,Moon RT.Wnt/β-catenin signaling promotes differentiation,not self-renewal,of human embryonic stem cells and is repressed by Oct4.Proc Natl Acad Sci U S A 2012;109:4485-4490[PMID:22392999 DOI:10.1073/pnas.1118777109]
98 Blauwkamp TA,Nigam S,Ardehali R,Weissman IL,Nusse R.Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors.Nat Commun 2012;3:1070[PMID:22990866 DOI:10.1038/ncomms2064]
99 Barker N,Ridgway RA,van Es JH,van de Wetering M,Begthel H,van den Born M,Danenberg E,Clarke AR,Sansom OJ,Clevers H.Crypt stem cells as the cells-of-origin of intestinal cancer.Nature2009;457:608-611[PMID:19092804 DOI:10.1038/nature07602]
100 Schepers AG,Snippert HJ,Stange DE,van den Born M,van Es JH,van de Wetering M,Clevers H.Lineage tracing reveals Lgr5+stem cell activity in mouse intestinal adenomas.Science 2012;337:730 -735[PMID:22855427 DOI:10.1126/science.1224676]
101 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]
102 Shackleton M,Vaillant F,Simpson KJ,Stingl J,Smyth GK,Asselin-Labat ML,Wu L,Lindeman GJ,Visvader JE.Generation of a functional mammary gland from a single stem cell.Nature 2006;439 :84-88[PMID:16397499]
103 Malanchi I,Santamaria-Martínez A,Susanto E,Peng H,Lehr HA,Delaloye JF,Huelsken J.Interactions between cancer stem cells and their niche govern metastatic colonization.Nature 2012;481:85-89[PMID:22158103 DOI:10.1038/nature10694]
104 Qu Q,Sun G,Li W,Yang S,Ye P,Zhao C,Yu RT,Gage FH,Evans RM,Shi Y.Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.Nat Cell Biol 2010;12:31-40;sup pp 1-9[PMID:20010817 DOI:10.1038/ncb2001]
105 Mazumdar J,O’Brien WT,Johnson RS,LaM anna JC,Chavez JC,Klein PS,Simon MC.O2 regulates stem cells through Wnt/β-catenin signalling.Nat Cell Biol 2010;12:1007-1013[PMID:20852629DOI:10.1038/ncb2102]
106 Santoyo-Ramos P,Likhatcheva M,García-Zepeda EA,Casta?eda-Patlán MC,Robles-Flores M.Hypoxia-inducible factors modulate the stemness and malignancy of colon cancer cells by playing opposite roles in canonical Wnt signaling.PLo S One 2014;9:e112580[PMID:25396735 DOI:10.1371/journal.pone.0112580]
107 Barakat MT,Humke EW,Scott MP.Learning from Jekyll to control Hyde:Hedgehog signaling in development and cancer.Trends Mol Med 2010;16:337-348[PMID:20696410 DOI:10 .1016/j.molmed.2010.05.003]
108 Wu SM,Choo AB,Yap MG,Chan KK.Role of Sonic hedgehog signaling and the expression of its components in human embryonic stem cells.Stem Cell Res 2010;4:38-49[PMID:19836325 DOI:10 .1016/j.scr.2009.09.002]
109 Heo JS,Lee MY,Han HJ.Sonic hedgehog stimulates mouse embryonic stem cell proliferation by cooperation of Ca2+/protein kinase C and epidermal growth factor receptor as well as Gli1activation.Stem Cells 2007;25:3069-3080[PMID:17901397 DOI:10 .1634/stemcells.2007-0550]
110 Scales SJ,de Sauvage FJ.Mechanisms of Hedgehog pathway activation in cancer and implications for therapy.Trends Pharmacol Sci 2009;30:303-312[PMID:19443052 DOI:10.1016/j.tips.2009.03.007]
111 Liu S,Dontu G,Mantle ID,Patel S,Ahn NS,Jackson KW,Suri P,Wicha MS.Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells.Cancer Res2006;66:6063-6071[PMID:16778178 DOI:10.1158/0008-5472.CAN-06-0054]
112 Clement V,Sanchez P,de Tribolet N,Radovanovic I,Ruiz i Altaba A.HEDGEHOG-GLI1 signaling regulates human glioma growth,cancer stem cell self-renewal,and tumorigenicity.Curr Biol 2007;17 :165-172[PMID:17196391 DOI:10.1016/j.cub.2006.11.033]
113 Bar EE,Chaudhry A,Lin A,Fan X,Schreck K,Matsui W,Piccirillo S,Vescovi AL,DiM eco F,Olivi A,Eberhart CG.Cyclopa-mine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma.Stem Cells 2007;25:2524-2533[PMID:17628016 DOI:10.1634/stemcells.2007-0166]
114 Merchant AA,Matsui W.Targeting Hedgehog--a cancer stem cell pathway.Clin Cancer Res 2010;16:3130-3140[PMID:20530699DOI:10.1158/1078-0432.CCR-09-2846]
115 Feldmann G,Dhara S,Fendrich V,Bedja D,Beaty R,Mullendore M,Karikari C,Alvarez H,Iacobuzio-Donahue C,Jimeno A,Gabrielson KL,Matsui W,Maitra A.Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases:a new paradigm for combination therapy in solid cancers.Cancer Res2007;67:2187-2196[PMID:17332349 DOI:10.1158/0008-5472.CAN-06-3281]
116 Chiba S.Notch signaling in stem cell systems.Stem Cells 2006;24:2437-2447[PMID:16888285 DOI:10.1634/stemcells.2005-0661]
117 Lowell S,Benchoua A,Heavey B,Smith AG.Notch promotes neural lineage entry by pluripotent embryonic stem cells.PLoS Biol2006;4:e121[PMID:16594731]
118 Noggle SA,Weiler D,Condie BG.Notch signaling is inactive but inducible in human embryonic stem cells.Stem Cells 2006;24:1646-1653[PMID:16614005 DOI:10.1634/stemcells.2005-0314]
119 Fox V,Gokhale PJ,Walsh JR,Matin M,Jones M,Andrews PW.Cell-cell signaling through NOTCH regulates human embryonic stem cell proliferation.Stem Cells 2008;26:715-723[PMID:18055449 DOI:10.1634/stemcells.2007-0368]
120 Yu X,Zou J,Ye Z,Hammond H,Chen G,Tokunaga A,Mali P,Li YM,Civin C,Gaiano N,Cheng L.Notch signaling activation in human embryonic stem cells is required for embryonic,but not trophoblastic,lineage commitment.Cell Stem Cell 2008;2:461-471[PMID:18462696 DOI:10.1016/j.stem.2008.03.001]
121 Liu J,Sato C,Cerletti M,Wagers A.Notch signaling in the regulation of stem cell self-renewal and differentiation.Curr Top Dev Biol 2010;92:367-409[PMID:20816402 DOI:10.1016/S0070-2153(10)92012-7]
122 Koch U,Lehal R,Radtke F.Stem cells living with a Notch.Development 2013;140:689-704[PMID:23362343 DOI:10.1242/dev.080614]
123 Abel EV,Kim EJ,Wu J,Hynes M,Bednar F,Proctor E,Wang L,Dziubinski ML,Simeone DM.The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer.PLo S One 2014;9:e91983[PMID:24647545 DOI:10.1371/journal.pone.0091983]
124 Hoey T,Yen WC,Axelrod F,Basi J,Donigian L,Dylla S,Fitch-Bruhns M,Lazetic S,Park IK,Sato A,Satyal S,Wang X,Clarke MF,Lewicki J,Gurney A.DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency.Cell Stem Cell 2009;5:168 -177[PMID:19664991 DOI:10.1016/j.stem.2009.05.019]
125 Sikandar SS,Pate KT,Anderson S,Dizon D,Edwards RA,Waterman ML,Lipkin SM.NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer.Cancer Res 2010;70:1469-1478[PMID:20145124 DOI:10.1158/0008-5472.CAN-09-2557]
126 Fan X,Matsui W,Khaki L,Stearns D,Chun J,Li YM,Eberhart CG.Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors.Cancer Res 2006;66:7445-7452[PMID:16885340]
127 Hallahan AR,Pritchard JI,Hansen S,Benson M,Stoeck J,Hatton BA,Russell TL,Ellenbogen RG,Bernstein ID,Beachy PA,Olson JM.The Smo A1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas.Cancer Res 2004;64:7794-7800[PMID:15520185]
128 Ayyanan A,Civenni G,Ciarloni L,Morel C,Mueller N,Lefort K,Mandinova A,Raffoul W,Fiche M,Dotto GP,Brisken C.Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism.Proc Natl Acad Sci USA 2006;103:3799-3804[PMID:16501043 DOI:10.1073/pnas.0600065103]
129 Farnie G,Clarke RB,Spence K,Pinnock N,Brennan K,Anderson NG,Bundred NJ.Novel cell culture technique for primary ductal carcinoma in situ:role of Notch and epidermal growth factor receptor signaling pathways.J Natl Cancer Inst 2007;99:616-627[PMID:17440163]
130 Harrison H,Farnie G,Howell SJ,Rock RE,Stylianou S,Brennan KR,Bundred NJ,Clarke RB.Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor.Cancer Res2010;70:709-718[PMID:20068161 DOI:10.1158/0008-5472.CAN-09-1681]
131 Gallahan D,Callahan R.Mammary tumorigenesis in feral mice:identification of a new int locus in mouse mammary tumor virus(Czech II)-induced mammary tumors.J Virol 1987;61:66-74[PMID:3023708]
132 Derynck R.TGF-beta-receptor-mediated signaling.Trends Biochem Sci 1994;19:548-553[PMID:7846768]
133 Oshimori N,Fuchs E.The harmonies played by TGF-βin stem cell biology.Cell Stem Cell 2012;11:751-764[PMID:23217421 DOI:10 .1016/j.stem.2012.11.001]
134 James D,Levine AJ,Besser D,Hemmati-Brivanlou A.TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells.Development 2005;132 :1273-1282[PMID:15703277]
135 Ogawa K,Saito A,Matsui H,Suzuki H,Ohtsuka S,Shimosato D,Morishita Y,Watabe T,Niwa H,Miyazono K.Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells.J Cell Sci 2007;120:55-65[PMID:17182901]
136 Vallier L,Alexander M,Pedersen RA.Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells.J Cell Sci 2005;118:4495-4509[PMID:16179608]
137 Qi X,Li TG,Hao J,Hu J,Wang J,Simmons H,Miura S,Mishina Y,Zhao GQ.BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways.Proc Natl Acad Sci USA 2004;101:6027-6032[PMID:15075392 DOI:10 .1073/pnas.0401367101]
138 Ying QL,Nichols J,Chambers I,Smith A.BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3.Cell 2003;115:281-292[PMID:14636556]
139 Xu RH,Chen X,Li DS,Li R,Addicks GC,Glennon C,Zwaka TP,Thomson JA.BMP4 initiates human embryonic stem cell differentiation to trophoblast.Nat Biotechnol 2002;20:1261-1264[PMID:12426580 DOI:10.1038/nbt761]
140 Xu RH,Peck RM,Li DS,Feng X,Ludwig T,Thomson JA.Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells.Nat Methods 2005;2:185-190[PMID:15782187]
141 Zhang P,Li J,Tan Z,Wang C,Liu T,Chen L,Yong J,Jiang W,Sun X,Du L,Ding M,Deng H.Short-term BMP-4 treatment initiates mesoderm induction in human embryonic stem cells.Blood 2008;111:1933-1941[PMID:18042803 DOI:10.1182/blood-2007-02-074120]
142 Brons IG,Smithers LE,Trotter MW,Rugg-Gunn P,Sun B,Chuva de Sousa Lopes SM,Howlett SK,Clarkson A,Ahrlund-Richter L,Pedersen RA,Vallier L.Derivation of pluripotent epiblast stem cells from mammalian embryos.Nature 2007;448:191-195[PMID:17597762 DOI:10.1038/nature05950]
143 Smith AG.Embryo-derived stem cells:of mice and men.Annu Rev Cell Dev Biol 2001;17:435-462[PMID:11687496 DOI:10.1146/annurev.cellbio.17.1.435]
144 Beattie GM,Lopez AD,Bucay N,Hinton A,Firpo MT,King CC,Hayek A.Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers.Stem Cells 2005;23:489 -495[PMID:15790770]
145 Xiao L,Yuan X,Sharkis SJ.Activin A maintains self-renewal and regulates fibroblast growth factor,Wnt,and bone morphogenic protein pathways in human embryonic stem cells.Stem Cells 2006;24 :1476-1486[PMID:16456129 DOI:10.1634/stemcells.2005-0299]
146 Vallier L,Reynolds D,Pedersen RA.Nodal inhibits differentiation of human embryonic stem cells along the neuroectodermal default pathway.Dev Biol 2004;275:403-421[PMID:15501227 DOI:10 .1016/j.ydbio.2004.08.031]
147 Vallier L,Mendjan S,Brown S,Chng Z,Teo A,Smithers LE,Trotter MW,Cho CH,Martinez A,Rugg-Gunn P,Brons G,Pedersen RA.Activin/Nodal signalling maintains pluripotency by controlling Nanog expression.Development 2009;136:1339-1349[PMID:19279133 DOI:10.1242/dev.033951]
148 Xu RH,Sampsell-Barron TL,Gu F,Root S,Peck RM,Pan G,Yu J,Antosiewicz-Bourget J,Tian S,Stewart R,Thomson JA.NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs.Cell Stem Cell 2008;3:196-206[PMID:18682241DOI:10.1016/j.stem.2008.07.001]
149 Mullen AC,Orlando DA,Newman JJ,Lovén J,Kumar RM,Bilodeau S,Reddy J,Guenther MG,De Koter RP,Young RA.Master transcription factors determine cell-type-specific responses to TGF-βsignaling.Cell 2011;147:565-576[PMID:22036565DOI:10.1016/j.cell.2011.08.050]
150 Besser D.Expression of nodal,lefty-a,and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3.J Biol Chem 2004;279:45076-45084[PMID:15308665 DOI:10.1074/jbc.M404979200]
151 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 epithelial-mesenchymal transition generates cells with properties of stem cells.Cell 2008;133:704-715[PMID:18485877 DOI:10.1016/j.cell.2008.03.027]
152 Yang J,Weinberg RA.Epithelial-mesenchymal transition:at the crossroads of development and tumor metastasis.Dev Cell 2008;14 :818-829[PMID:18539112 DOI:10.1016/j.devcel.2008.05.009]
153 MassaguéJ.TGFbeta in Cancer.Cell 2008;134:215-230[PMID:18662538 DOI:10.1016/j.cell.2008.07.001]
154 Guasch G,Schober M,Pasolli HA,Conn EB,Polak L,Fuchs E.Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia.Cancer Cell 2007;12 :313-327[PMID:17936557 DOI:10.1016/j.ccr.2007.08.020]
155 Mc Lean GW,Komiyama NH,Serrels B,Asano H,Reynolds L,Conti F,Hodivala-Dilke K,Metzger D,Chambon P,Grant SG,Frame MC.Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression.Genes Dev2004;18:2998-3003[PMID:15601818]
156 Schober M,Fuchs E.Tumor-initiating stem cells of squamous cell carcinomas and their control by TGF-βand integrin/focal adhesion kinase(FAK)signaling.Proc Natl Acad Sci USA 2011;108:10544-10549[PMID:21670270 DOI:10.1073/pnas.1107807108]
157 Bhola NE,Balko JM,Dugger TC,Kuba MG,Sánchez V,Sanders M,Stanford J,Cook RS,Arteaga CL.TGF-βinhibition enhances chemotherapy action against triple-negative breast cancer.J Clin Invest 2013;123:1348-1358[PMID:23391723 DOI:10.1172/JCI65416]
158 Pe?uelas S,Anido J,Prieto-Sánchez RM,Folch G,Barba I,Cuartas I,García-Dorado D,Poca MA,Sahuquillo J,Baselga J,Seoane J.TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma.Cancer Cell 2009;15:315 -327[PMID:19345330 DOI:10.1016/j.ccr.2009.02.011]
159 Ikushima H,Todo T,Ino Y,Takahashi M,Miyazawa K,Miyazono K.Autocrine TGF-beta signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors.Cell Stem Cell 2009;5:504-514[PMID:19896441 DOI:10.1016/j.stem.2009.08.018]
160 Piccirillo SG,Reynolds BA,Zanetti N,Lamorte G,Binda E,Broggi G,Brem H,Olivi A,Dimeco F,Vescovi AL.Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.Nature 2006;444:761-765[PMID:17151667]
161 Lee J,Son MJ,Woolard K,Donin NM,Li A,Cheng CH,Kotliarova S,Kotliarov Y,Walling J,Ahn S,Kim M,Totonchy M,Cusack T,Ene C,Ma H,Su Q,Zenklusen JC,Zhang W,Maric D,Fine HA.Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells.Cancer Cell 2008;13:69-80[PMID:18167341 DOI:10.1016/j.ccr.2007.12.005]
162 Lanner F,Rossant J.The role of FGF/Erk signaling in pluripotent cells.Development 2010;137:3351-3360[PMID:20876656 DOI:10 .1242/dev.050146]
163 Turner N,Grose R.Fibroblast growth factor signalling:from development to cancer.Nat Rev Cancer 2010;10:116-129[PMID:20094046 DOI:10.1038/nrc2780]
164 Kunath T,Saba-El-Leil MK,Almousailleakh M,Wray J,Meloche S,Smith A.FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment.Development 2007;134:2895-2902[PMID:17660198]
165 Stavridis MP,Lunn JS,Collins BJ,Storey KG.A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification.Development 2007;134:2889-2894[PMID:17660197]
166 Ying QL,Wray J,Nichols J,Batlle-Morera L,Doble B,Woodgett J,Cohen P,Smith A.The ground state of embryonic stem cell self-renewal.Nature 2008;453:519-523[PMID:18497825 DOI:10 .1038/nature06968]
167 Toyooka Y,Shimosato D,Murakami K,Takahashi K,Niwa H.Identification and characterization of subpopulations in undifferentiated ES cell culture.Development 2008;135:909-918[PMID:18263842 DOI:10.1242/dev.017400]
168 Amit M,Carpenter MK,Inokuma MS,Chiu CP,Harris CP,Waknitz MA,Itskovitz-Eldor J,Thomson JA.Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture.Dev Biol 2000;227:271 -278[PMID:11071754 DOI:10.1006/dbio.2000.9912]
169 Xu C,Inokuma MS,Denham J,Golds K,Kundu P,Gold JD,Carpenter MK.Feeder-free growth of undifferentiated human embryonic stem cells.Nat Biotechnol 2001;19:971-974[PMID:11581665 DOI:10.1038/nbt1001-971]
170 Wang G,Zhang H,Zhao Y,Li J,Cai J,Wang P,Meng S,Feng J,Miao C,Ding M,Li D,Deng H.Noggin and b FGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers.Biochem Biophys Res Commun 2005;330:934 -942[PMID:15809086 DOI:10.1016/j.bbrc.2005.03.058]
171 Armstrong L,Hughes O,Yung S,Hyslop L,Stewart R,Wappler I,Peters H,Walter T,Stojkovic P,Evans J,Stojkovic M,Lako M.The role of PI3K/AKT,MAPK/ERK and NFkappabeta signalling in the maintenance of human embryonic stem cell pluripotency and viability highlighted by transcriptional profiling and functional analysis.Hum Mol Genet 2006;15:1894-1913[PMID:16644866]
172 Ding VM,Ling L,Natarajan S,Yap MG,Cool SM,Choo AB.FGF-2 modulates Wnt signaling in undifferentiated hE SC and iP S cells through activated PI3-K/GSK3beta signaling.J Cell Physiol2010;225:417-428[PMID:20506199 DOI:10.1002/jcp.22214]
173 Li J,Wang G,Wang C,Zhao Y,Zhang H,Tan Z,Song Z,Ding M,Deng H.MEK/ERK signaling contributes to the maintenance of human embryonic stem cell self-renewal.Differentiation 2007;75:299 -307[PMID:17286604 DOI:10.1111/j.1432-0436.2006.00143.x]
174 Li W,Wei W,Zhu S,Zhu J,Shi Y,Lin T,Hao E,Hayek A,Deng H,Ding S.Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors.Cell Stem Cell 2009;4:16-19[PMID:19097958 DOI:10.1016/j.stem.2008.11.014]
175 Xu Y,Zhu X,Hahm HS,Wei W,Hao E,Hayek A,Ding S.Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules.Proc Natl Acad Sci USA 2010;107:8129-8134[PMID:20406903 DOI:10 .1073/pnas.1002024107]
176 Niwa H,Ogawa K,Shimosato D,Adachi K.A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells.Nature 2009;460:118-122[PMID:19571885 DOI:10.1038/nature08113]
177 Dirks PB.Brain tumor stem cells:bringing order to the chaos of brain cancer.J Clin Oncol 2008;26:2916-2924[PMID:18539973DOI:10.1200/JCO.2008.17.6792]
178 Ponti D,Costa A,Zaffaroni N,Pratesi G,Petrangolini G,Coradini D,Pilotti S,Pierotti MA,Daidone MG.Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties.Cancer Res 2005;65:5506-5511[PMID:15994920DOI:10.1158/0008-5472.CAN-05-0626]
179 Fillmore CM,Gupta PB,Rudnick JA,Caballero S,Keller PJ,Lander ES,Kuperwasser C.Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling.Proc Natl Acad Sci USA 2010;107:21737-21742[PMID:21098263 DOI:10.1073/pnas.1007863107]
180 Guthridge MA,Seldin M,Basilico C.Induction of expression of growth-related genes by FGF-4 in mouse fibroblasts.Oncogene1996;12:1267-1278[PMID:8649829]
181 Fu M,Wang C,Li Z,Sakamaki T,Pestell RG.Minireview:Cyclin D1:normal and abnormal functions.Endocrinology 2004;145:5439-5447[PMID:15331580 DOI:10.1210/en.2004-0959]
182 McK eon F.p63 and the epithelial stem cell:more than status quo?Genes Dev 2004;18:465-469[PMID:15037544 DOI:10.1101/gad.1190504]
183 Kosaka N,Sakamoto H,Terada M,Ochiya T.Pleiotropic function of FGF-4:its role in development and stem cells.Dev Dyn 2009;238 :265-276[PMID:18792115 DOI:10.1002/dvdy.21699]
184 Loh YH,Wu Q,Chew JL,Vega VB,Zhang W,Chen X,Bourque G,George J,Leong B,Liu J,Wong KY,Sung KW,Lee CW,Zhao XD,Chiu KP,Lipovich L,Kuznetsov VA,Robson P,Stanton LW,Wei CL,Ruan Y,Lim B,Ng HH.The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.Nat Genet 2006;38:431-440[PMID:16518401 DOI:10.1038/ng1760]
185 Jaenisch R,Young R.Stem cells,the molecular circuitry of pluripotency and nuclear reprogramming.Cell 2008;132:567-582[PMID:18295576 DOI:10.1016/j.cell.2008.01.015]
186 Boyer LA,Plath K,Zeitlinger J,Brambrink T,Medeiros LA,Lee TI,Levine SS,Wernig M,Tajonar A,Ray MK,Bell GW,Otte AP,Vidal M,Gifford DK,Young RA,Jaenisch R.Polycomb complexes repress developmental regulators in murine embryonic stem cells.Nature 2006;441:349-353[PMID:16625203 DOI:10.1038/nature04733]
187 Orkin SH,Hochedlinger K.Chromatin connections to pluripotency and cellular reprogramming.Cell 2011;145:835-850[PMID:21663790 DOI:10.1016/j.cell.2011.05.019]
188 Young RA.Control of the embryonic stem cell state.Cell 2011;144 :940-954[PMID:21414485 DOI:10.1016/j.cell.2011.01.032]
189 Kim J,Woo AJ,Chu J,Snow JW,Fujiwara Y,Kim CG,Cantor AB,Orkin SH.A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs.Cell 2010;143 :313-324[PMID:20946988 DOI:10.1016/j.cell.2010.09.010]
190 Orkin SH,Wang J,Kim J,Chu J,Rao S,Theunissen TW,Shen X,Levasseur DN.The transcriptional network controlling pluripotency in ES cells.Cold Spring Harb Symp Quant Biol 2008;73:195-202[PMID:19478325 DOI:10.1101/sqb.2008.72.001]
191 Chen X,Xu H,Yuan P,Fang F,Huss M,Vega VB,Wong E,Orlov YL,Zhang W,Jiang J,Loh YH,Yeo HC,Yeo ZX,Narang V,Govindarajan KR,Leong B,Shahab A,Ruan Y,Bourque G,Sung WK,Clarke ND,Wei CL,Ng HH.Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.Cell 2008;133:1106-1117[PMID:18555785 DOI:10.1016/j.cell.2008.04.043]
192 Hnisz D,Abraham BJ,Lee TI,Lau A,Saint-AndréV,Sigova AA,Hoke HA,Young RA.Super-enhancers in the control of cell identity and disease.Cell 2013;155:934-947[PMID:24119843DOI:10.1016/j.cell.2013.09.053]
193 Whyte WA,Orlando DA,Hnisz D,Abraham BJ,Lin CY,Kagey MH,Rahl PB,Lee TI,Young RA.Master transcription factors and mediator establish super-enhancers at key cell identity genes.Cell 2013;153:307-319[PMID:23582322 DOI:10.1016/j.cell.2013.03.035]
194 Takahashi K,Yamanaka S.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell 2006;126:663-676[PMID:16904174]
195 Rosner MH,Vigano MA,Ozato K,Timmons PM,Poirier F,Rigby PW,Staudt LM.A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo.Nature 1990;345:686 -692[PMID:1972777 DOI:10.1038/345686a0]
196 Sch?ler HR,Dressler GR,Balling R,Rohdewohld H,Gruss P.Oct4:a germline-specific transcription factor mapping to the mouse t-complex.EMBO J 1990;9:2185-2195[PMID:2357966]
197 Cauffman G,Van de Velde H,Liebaers I,Van Steirteghem A.Oct4 mR NA and protein expression during human preimplantation development.Mol Hum Reprod 2005;11:173-181[PMID:15695770]
198 Nichols J,Zevnik B,Anastassiadis K,Niwa H,Klewe-Nebenius D,Chambers I,Sch?ler H,Smith A.Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.Cell 1998;95:379-391[PMID:9814708]
199 Nichols J,Evans EP,Smith AG.Establishment of germ-line-competent embryonic stem(ES)cells using differentiation inhibiting activity.Development 1990;110:1341-1348[PMID:2129226]
200 Niwa H,Miyazaki J,Smith AG.Quantitative expression of Oct-3/4 defines differentiation,dedifferentiation or self-renewal of ES cells.Nat Genet 2000;24:372-376[PMID:10742100 DOI:10 .1038/74199]
201 Shimozaki K,Nakashima K,Niwa H,Taga T.Involvement of Oct3/4 in the enhancement of neuronal differentiation of ES cells in neurogenesis-inducing cultures.Development 2003;130:2505-2512[PMID:12702663]
202 Aksoy I,Jauch R,Chen J,Dyla M,Divakar U,Bogu GK,Teo R,Leng Ng CK,Herath W,Lili S,Hutchins AP,Robson P,Kolatkar PR,Stanton LW.Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm.EMBO J 2013;32 :938-953[PMID:23474895 DOI:10.1038/emboj.2013.31]
203 Atlasi Y,Mowla SJ,Ziaee SA,Bahrami AR.Oct4,an embryonic stem cell marker,is highly expressed in bladder cancer.Int J Cancer2007;120:1598-1602[PMID:17205510 DOI:10.1002/ijc.22508]
204 Ezeh UI,Turek PJ,Reijo RA,Clark AT.Human embryonic stem cell genes OCT4,NANOG,STELLAR,and GDF3 are expressed in both seminoma and breast carcinoma.Cancer 2005;104:2255-2265[PMID:16228988 DOI:10.1002/cncr.21432]
205 Gu G,Yuan J,Wills M,Kasper S.Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo.Cancer Res 2007;67:4807-4815[PMID:17510410]
206 Liu CG,Lu Y,Wang BB,Zhang YJ,Zhang RS,Lu Y,Chen B,Xu H,Jin F,Lu P.Clinical implications of stem cell gene Oct4 expression in breast cancer.Ann Surg 2011;253:1165-1171[PMID:21394007DOI:10.1097/SLA.0b013e318214c54e]
207 Hu T,Liu S,Breiter DR,Wang F,Tang Y,Sun S.Octamer 4 small interfering RNA results in cancer stem cell-like cell apoptosis.Cancer Res 2008;68:6533-6540[PMID:18701476 DOI:10 .1158/0008-5472.CAN-07-6642]
208 Chiou SH,Yu CC,Huang CY,Lin SC,Liu CJ,Tsai TH,Chou SH,Chien CS,Ku HH,Lo JF.Positive correlations of Oct4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma.Clin Cancer Res 2008;14:4085-4095[PMID:18593985 DOI:10.1158/1078-0432.CCR-07-4404]
209 Rentala S,Mangamoori LN.Oct4 expression maintained stem cell properties in prostate cancer-derived cd133 mdr1 cells.Trop J Pharm Res 2009;8:3-9
210 Beltran AS,Rivenbark AG,Richardson BT,Yuan X,Quian H,Hunt JP,Zimmerman E,Graves LM,Blancafort P.Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription factor.Breast Cancer Res 2011;13:R94[PMID:21952072 DOI:10 .1186/bcr3019]
211 Wang YD,Cai N,Wu XL,Cao HZ,Xie LL,Zheng PS.OCT4promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway.Cell Death Dis 2013;4:e760[PMID:23928699 DOI:10.1038/cddis.2013.272]
212 Koo BS,Lee SH,Kim JM,Huang S,Kim SH,Rho YS,Bae WJ,Kang HJ,Kim YS,Moon JH,Lim YC.Oct4 is a critical regulator of stemness in head and neck squamous carcinoma cells.Oncogene 2015;34:2317-2324[PMID:24954502 DOI:10.1038/onc.2014.174]
213 Kamachi Y,Uchikawa M,Kondoh H.Pairing SOX off:with partners in the regulation of embryonic development.Trends Genet2000;16:182-187[PMID:10729834]
214 Avilion AA,Nicolis SK,Pevny LH,Perez L,Vivian N,Lovell-Badge R.Multipotent cell lineages in early mouse development depend on SOX2 function.Genes Dev 2003;17:126-140[PMID:12514105 DOI:10.1101/gad.224503]
215 Masui S,Nakatake Y,Toyooka Y,Shimosato D,Yagi R,Takahashi K,Okochi H,Okuda A,Matoba R,Sharov AA,Ko MS,Niwa H.Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells.Nat Cell Biol 2007;9:625-635[PMID:17515932]
216 Boer B,Kopp J,Mallanna S,Desler M,Chakravarthy H,Wilder PJ,Bernadt C,Rizzino A.Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes.Nucleic Acids Res 2007;35:1773-1786[PMID:17324942]
217 Kopp JL,Ormsbee BD,Desler M,Rizzino A.Small increases in the level of Sox2 trigger the differentiation of mouse embryonic stem cells.Stem Cells 2008;26:903-911[PMID:18238855 DOI:10 .1634/stemcells.2007-0951]
218 Basu-Roy U,Seo E,Ramanathapuram L,Rapp TB,Perry JA,Orkin SH,Mansukhani A,Basilico C.Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas.Oncogene 2012;31:2270-2282[PMID:21927024 DOI:10.1038/onc.2011.405]
219 Lou X,Han X,Jin C,Tian W,Yu W,Ding D,Cheng L,Huang B,Jiang H,Lin B.SOX2 targets fibronectin 1 to promote cell migration and invasion in ovarian cancer:new molecular leads for therapeutic intervention.OMICS 2013;17:510-518[PMID:23895273 DOI:10.1089/omi.2013.0058]
220 Tian T,Zhang Y,Wang S,Zhou J,Xu S.Sox2 enhances the tumorigenicity and chemoresistance of cancer stem-like cells derived from gastric cancer.J Biomed Res 2012;26:336-345[PMID:23554769 DOI:10.7555/JBR.26.20120045]
221 Herreros-Villanueva M,Zhang JS,Koenig A,Abel EV,Smyrk TC,Bamlet WR,de Narvajas AA,Gomez TS,Simeone DM,Bujanda L,Billadeau DD.SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells.Oncogenesis 2013;2:e61[PMID:23917223 DOI:10.1038/oncsis.2013.23]
222 Rybak AP,Tang D.SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells.Cell Signal 2013;25:2734-2742[PMID:24036214 DOI:10.1016/j.cellsig.2013.08.041]
223 Singh S,Trevino J,Bora-Singhal N,Coppola D,Haura E,Altiok S,Chellappan SP.EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer.Mol Cancer 2012;11:73[PMID:23009336 DOI:10 .1186/1476-4598-11-73]
224 Santini R,Pietrobono S,Pandolfi S,Montagnani V,D’Amico M,Penachioni JY,Vinci MC,Borgognoni L,Stecca B.SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells.Oncogene 2014;33:4697-4708[PMID:24681955 DOI:10 .1038/onc.2014.71]
225 Favaro R,Appolloni I,Pellegatta S,Sanga AB,Pagella P,Gambini E,Pisati F,Ottolenghi S,Foti M,Finocchiaro G,Malatesta P,Nicolis SK.Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma.Cancer Res 2014;74 :1833-1844[PMID:24599129 DOI:10.1158/0008-5472.CAN-13-1942]
226 Chambers I,Silva J,Colby D,Nichols J,Nijmeijer B,Robertson M,Vrana J,Jones K,Grotewold L,Smith A.Nanog safeguards pluripotency and mediates germline development.Nature 2007;450 :1230-1234[PMID:18097409 DOI:10.1038/nature06403]
227 Mitsui K,Tokuzawa Y,Itoh H,Segawa K,Murakami M,Takahashi K,Maruyama M,Maeda M,Yamanaka S.The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells.Cell 2003;113:631-642[PMID:12787504]
228 Chambers I,Colby D,Robertson M,Nichols J,Lee S,Tweedie S,Smith A.Functional expression cloning of Nanog,a pluripotency sustaining factor in embryonic stem cells.Cell 2003;113:643-655[PMID:12787505]
229 Silva J,Nichols J,Theunissen TW,Guo G,van Oosten AL,Barrandon O,Wray J,Yamanaka S,Chambers I,Smith A.Nanog is the gateway to the pluripotent ground state.Cell 2009;138:722-737[PMID:19703398 DOI:10.1016/j.cell.2009.07.039]
230 Hyslop L,Stojkovic M,Armstrong L,Walter T,Stojkovic P,Przyborski S,Herbert M,Murdoch A,Strachan T,Lako M.Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages.Stem Cells 2005;23:1035-1043[PMID:15983365 DOI:10.1634/stemcells.2005-0080]
231 Kuroda T,Tada M,Kubota H,Kimura H,Hatano SY,Suemori H,Nakatsuji N,Tada T.Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression.Mol Cell Biol 2005;25:2475-2485[PMID:15743839 DOI:10.1128/MCB.25.6.2475-2485.2005]
232 Amsterdam A,Raanan C,Schreiber L,Freyhan O,Schechtman L,Givol D.Localization of the stem cell markers LGR5 and Nanog in the normal and the cancerous human ovary and their inter-relationship.Acta Histochem 2013;115:330-338[PMID:23092806DOI:10.1016/j.acthis.2012.09.004]
233 Bussolati B,Bruno S,Grange C,Ferrando U,Camussi G.Identi-fication of a tumor-initiating stem cell population in human renal carcinomas.FASEB J 2008;22:3696-3705[PMID:18614581 DOI:10 .1096/fj.08-102590]
234 Chiou SH,Wang ML,Chou YT,Chen CJ,Hong CF,Hsieh WJ,Chang HT,Chen YS,Lin TW,Hsu HS,Wu CW.Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation.Cancer Res 2010;70:10433-10444[PMID:21159654 DOI:10.1158/0008-5472.can-10-2638]
235 Lu X,Mazur SJ,Lin T,Appella E,Xu Y.The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis.Oncogene 2014;33:2655-2664[PMID:23770853 DOI:10.1038/onc.2013.209]
236 Guo Y,Liu S,Wang P,Zhao S,Wang F,Bing L,Zhang Y,Ling EA,Gao J,Hao A.Expression profile of embryonic stem cell-associated genes Oct4,Sox2 and Nanog in human gliomas.Histopathology 2011;59:763-775[PMID:22014056 DOI:10.1111/j.1365-2559.2011.03993.x]
237 Lin T,Ding YQ,Li JM.Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma.Med Oncol 2012;29:878-885[PMID:21336986 DOI:10.1007/s12032-011-9860-9]
238 Lee M,Nam EJ,Kim SW,Kim S,Kim JH,Kim YT.Prognostic impact of the cancer stem cell-related marker NANOG in ovarian serous carcinoma.Int J Gynecol Cancer 2012;22:1489-1496[PMID:23095773 DOI:10.1097/IGJ.0b013e3182738307]
239 Meng HM,Zheng P,Wang XY,Liu C,Sui HM,Wu SJ,Zhou J,Ding YQ,Li J.Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer.Cancer Biol Ther 2010;9:295-302[PMID:20026903 DOI:10.4161/cbt.9.4.10666]
240 Nagata T,Shimada Y,Sekine S,Hori R,Matsui K,Okumura T,Sawada S,Fukuoka J,Tsukada K.Prognostic significance of NANOG and KLF4 for breast cancer.Breast Cancer 2014;21:96 -101[PMID:22528804 DOI:10.1007/s12282-012-0357-y]
241 Ibrahim EE,Babaei-Jadidi R,Saadeddin A,Spencer-Dene B,Hossaini S,Abuzinadah M,Li N,Fadhil W,Ilyas M,Bonnet D,Nateri AS.Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1-and TCF-dependent mechanisms.Stem Cells 2012;30:2076-2087[PMID:22851508DOI:10.1002/stem.1182]
242 Jeter CR,Liu B,Liu X,Chen X,Liu C,Calhoun-Davis T,Repass J,Zaehres H,Shen JJ,Tang DG.NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation.Oncogene 2011;30:3833-3845[PMID:21499299DOI:10.1038/onc.2011.114]
243 Lee TK,Castilho A,Cheung VC,Tang KH,Ma S,Ng IO.CD24(+)liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation.Cell Stem Cell 2011;9 :50-63[PMID:21726833 DOI:10.1016/j.stem.2011.06.005]
244 Niu CS,Li DX,Liu YH,Fu XM,Tang SF,Li J.Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells.Oncol Rep 2011;26:593-601[PMID:21573506 DOI:10 .3892/or.2011.1308]
245 Zbinden M,Duquet A,Lorente-Trigos A,Ngwabyt SN,Borges I,Ruiz i Altaba A.NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1and p53.EMBO J 2010;29:2659-2674[PMID:20581802 DOI:10 .1038/emboj.2010.137]
246 Zhou X,Zhou YP,Huang GR,Gong BL,Yang B,Zhang DX,Hu P,Xu SR.Expression of the stem cell marker,Nanog,in human endometrial adenocarcinoma.Int J Gynecol Pathol 2011;30:262 -270[PMID:21464727 DOI:10.1097/PGP.0b013e3182055a1f]
247 Wang ML,Chiou SH,Wu CW.Targeting cancer stem cells:emerging role of Nanog transcription factor.Onco Targets Ther2013;6:1207-1220[PMID:24043946 DOI:10.2147/OTT.S38114]
248 He A,Qi W,Huang Y,Feng T,Chen J,Sun Y,Shen Z,Yao Y.CD133 expression predicts lung metastasis and poor prognosis in osteosarcoma patients:A clinical and experimental study.Exp Ther Med 2012;4:435-441[PMID:23181114 DOI:10.3892/etm.2012.603]
249 Leung EL,Fiscus RR,Tung JW,Tin VP,Cheng LC,Sihoe AD,Fink LM,Ma Y,Wong MP.Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties.PLoS One 2010;5:e14062[PMID:21124918 DOI:10.1371/journal.pone.0014062]
250 Han J,Zhang F,Yu M,Zhao P,Ji W,Zhang H,Wu B,Wang Y,Niu R.RNA interference-mediated silencing of NANOG reduces cell proliferation and induces G0/G1 cell cycle arrest in breast cancer cells.Cancer Lett 2012;321:80-88[PMID:22381696 DOI:10 .1016/j.canlet.2012.02.021]
251 Siu MK,Wong ES,Kong DS,Chan HY,Jiang L,Wong OG,Lam EW,Chan KK,Ngan HY,Le XF,Cheung AN.Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and Fox J1 and contributes to adverse clinical outcome in ovarian cancers.Oncogene 2013;32:3500-3509[PMID:22945654 DOI:10.1038/onc.2012.363]
252 Bourillot PY,Aksoy I,Schreiber V,Wianny F,Schulz H,Hummel O,Hubner N,Savatier P.Novel STAT3 target genes exert distinct roles in the inhibition of mesoderm and endoderm differentiation in cooperation with Nanog.Stem Cells 2009;27:1760-1771[PMID:19544440 DOI:10.1002/stem.110]
253 Ghaleb AM,Nandan MO,Chanchevalap S,Dalton WB,Hisamuddin IM,Yang VW.Krüppel-like factors 4 and 5:the yin and yang regulators of cellular proliferation.Cell Res 2005;15:92 -96[PMID:15740636]
254 Bourillot PY,Savatier P.Krüppel-like transcription factors and control of pluripotency.BMC Biol 2010;8:125[PMID:20875146DOI:10.1186/1741-7007-8-125]
255 Ivanova N,Dobrin R,Lu R,Kotenko I,Levorse J,De Coste C,Schafer X,Lun Y,Lemischka IR.Dissecting self-renewal in stem cells with RNA interference.Nature 2006;442:533-538[PMID:16767105]
256 Li Y,Mc Clintick J,Zhong L,Edenberg HJ,Yoder MC,Chan RJ.Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4.Blood 2005;105:635-637[PMID:15358627 DOI:10.1182/blood-2004-07-2681]
257 Nakatake Y,Fukui N,Iwamatsu Y,Masui S,Takahashi K,Yagi R,Yagi K,Miyazaki J,Matoba R,Ko MS,Niwa H.Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells.Mol Cell Biol 2006;26:7772-7782[PMID:16954384 DOI:10.1128/MCB.00468-06]
258 Jiang J,Chan YS,Loh YH,Cai J,Tong GQ,Lim CA,Robson P,Zhong S,Ng HH.A core Klf circuitry regulates self-renewal of embryonic stem cells.Nat Cell Biol 2008;10:353-360[PMID:18264089 DOI:10.1038/ncb1698]
259 Yasunaga M,Tada S,Torikai-Nishikawa S,Nakano Y,Okada M,Jakt LM,Nishikawa S,Chiba T,Era T,Nishikawa S.Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells.Nat Biotechnol 2005;23:1542-1550[PMID:16311587 DOI:10.1038/nbt1167]
260 Aksoy I,Giudice V,Delahaye E,Wianny F,Aubry M,Mure M,Chen J,Jauch R,Bogu GK,Nolden T,Himmelbauer H,Xavier Doss M,Sachinidis A,Schulz H,Hummel O,Martinelli P,Hübner N,Stanton LW,Real FX,Bourillot PY,Savatier P.Klf4 and Klf5differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells.Nat Commun 2014;5:3719[PMID:24770696 DOI:10.1038/ncomms4719]
261 Wong CW,Hou PS,Tseng SF,Chien CL,Wu KJ,Chen HF,Ho HN,Kyo S,Teng SC.Krüppel-like transcription factor 4 contributes to maintenance of telomerase activity in stem cells.Stem Cells2010;28:1510-1517[PMID:20629177 DOI:10.1002/stem.477]
262 Hoffmeyer K,Raggioli A,Rudloff S,Anton R,Hierholzer A,Del Valle I,Hein K,Vogt R,Kemler R.Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells.Science 2012;336 :1549-1554[PMID:22723415 DOI:10.1126/science.1218370]
263 Yu F,Li J,Chen H,Fu J,Ray S,Huang S,Zheng H,Ai W.Kruppel-like factor 4(KLF4)is required for maintenance of breast cancer stem cells and for cell migration and invasion.Oncogene 2011;30:2161-2172[PMID:21242971 DOI:10.1038/onc.2010.591]
264 Yu T,Chen X,Zhang W,Li J,Xu R,Wang TC,Ai W,Liu C.Krüppel-like factor 4 regulates intestinal epithelial cell morphology and polarity.PLoS One 2012;7:e32492[PMID:22384261 DOI:10 .1371/journal.pone.0032492]
265 Yori JL,Johnson E,Zhou G,Jain MK,Keri RA.Kruppel-like factor 4 inhibits epithelial-to-mesenchymal transition through regulation of E-cadherin gene expression.J Biol Chem 2010;285:16854-16863[PMID:20356845 DOI:10.1074/jbc.M110.114546]
266 Leng Z,Tao K,Xia Q,Tan J,Yue Z,Chen J,Xi H,Li J,Zheng H.Krüppel-like factor 4 acts as an oncogene in colon cancer stem cell-enriched spheroid cells.PLo S One 2013;8:e56082[PMID:23418515 DOI:10.1371/journal.pone.0056082]
267 Wellner U,Schubert J,Burk UC,Schmalhofer O,Zhu F,Sonntag A,Waldvogel B,Vannier C,Darling D,zur Hausen A,Brunton VG,Morton J,Sansom O,Schüler J,Stemmler MP,Herzberger C,Hopt U,Keck T,Brabletz S,Brabletz T.The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microR NAs.Nat Cell Biol 2009;11:1487-1495[PMID:19935649DOI:10.1038/ncb1998]
268 Okuda H,Xing F,Pandey PR,Sharma S,Watabe M,Pai SK,Mo YY,Iiizumi-Gairani M,Hirota S,Liu Y,Wu K,Pochampally R,Watabe K.miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4.Cancer Res 2013;73:1434-1444[PMID:23384942 DOI:10.1158/0008-5472.CAN-12-2037]
269 Ma J,Yao Y,Wang P,Liu Y,Zhao L,Li Z,Li Z,Xue Y.MiR-152functions as a tumor suppressor in glioblastoma stem cells by targeting Krüppel-like factor 4.Cancer Lett 2014;355:85-95[PMID:25218589 DOI:10.1016/j.canlet.2014.09.012]
270 Cole MD,Henriksson M.25 years of the c-Myc oncogene.Semin Cancer Biol 2006;16:241[PMID:16935523]
271 Laurenti E,Wilson A,Trumpp A.Myc’s other life:stem cells and beyond.Curr Opin Cell Biol 2009;21:844-854[PMID:19836223DOI:10.1016/j.ceb.2009.09.006]
272 Meyer N,Kim SS,Penn LZ.The Oscar-worthy role of Myc in apoptosis.Semin Cancer Biol 2006;16:275-287[PMID:16945552]
273 Cartwright P,McL ean C,Sheppard A,Rivett D,Jones K,Dalton S.LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism.Development 2005;132:885-896[PMID:15673569]
274 Smith KN,Singh AM,Dalton S.Myc represses primitive endoderm differentiation in pluripotent stem cells.Cell Stem Cell 2010;7:343 -354[PMID:20804970 DOI:10.1016/j.stem.2010.06.023]
275 Chappell J,Sun Y,Singh A,Dalton S.MYC/MAX control ERK signaling and pluripotency by regulation of dual-specificity phosphatases 2 and 7.Genes Dev 2013;27:725-733[PMID:23592794 DOI:10.1101/gad.211300.112]
276 Kidder BL,Yang J,Palmer S.Stat3 and c-Myc genome-wide promoter occupancy in embryonic stem cells.PLoS One 2008;3:e3932[PMID:19079543 DOI:10.1371/journal.pone.0003932]
277 Kim J,Chu J,Shen X,Wang J,Orkin SH.An extended transcriptional network for pluripotency of embryonic stem cells.Cell 2008;132:1049-1061[PMID:18358816 DOI:10.1016/j.cell.2008.02.039]
278 Sridharan R,Tchieu J,Mason MJ,Yachechko R,Kuoy E,Horvath S,Zhou Q,Plath K.Role of the murine reprogramming factors in the induction of pluripotency.Cell 2009;136:364-377[PMID:19167336 DOI:10.1016/j.cell.2009.01.001]
279 Yin XY,Grove L,Datta NS,Katula K,Long MW,Prochownik EV.Inverse regulation of cyclin B1 by c-Myc and p53 and induction of tetraploidy by cyclin B1 overexpression.Cancer Res 2001;61:6487-6493[PMID:11522645]
280 Eilers M,Eisenman RN.Myc’s broad reach.Genes Dev 2008;22:2755-2766[PMID:18923074 DOI:10.1101/gad.1712408]
281 Zheng H,Ying H,Yan H,Kimmelman AC,Hiller DJ,Chen AJ,Perry SR,Tonon G,Chu GC,Ding Z,Stommel JM,Dunn KL,Wiedemeyer R,You MJ,Brennan C,Wang YA,Ligon KL,Wong WH,Chin L,de Pinho RA.Pten and p53 converge on c-Myc to control differentiation,self-renewal,and transformation of normal and neoplastic stem cells in glioblastoma.Cold Spring Harb Symp Quant Biol 2008;73:427-437[PMID:19150964 DOI:10.1101/sqb.2008.73.047]
282 Ho C,Wang C,Mattu S,Destefanis G,Ladu S,Delogu S,Armbruster J,Fan L,Lee SA,Jiang L,Dombrowski F,Evert M,Chen X,Calvisi DF.AKT(v-akt murine thymoma viral oncogene homolog 1)and N-Ras(neuroblastoma ras viral oncogene homolog)coactivation in the mouse liver promotes rapid carcinogenesis by way of m TOR(mammalian target of rapamycin complex 1 ),FOXM1(forkhead box M1)/SKP2,and c-Myc pathways.Hepatology 2012;55:833-845[PMID:21993994 DOI:10.1002/hep.24736]
283 Wang J,Wang H,Li Z,Wu Q,Lathia JD,Mc Lendon RE,Hjelmeland AB,Rich JN.c-Myc is required for maintenance of glioma cancer stem cells.PLo S One 2008;3:e3769[PMID:19020659 DOI:10.1371/journal.pone.0003769]
284 Salcido CD,Larochelle A,Taylor BJ,Dunbar CE,Varticovski L.Molecular characterisation of side population cells with cancer stem cell-like characteristics in small-cell lung cancer.Br J Cancer 2010;102 :1636-1644[PMID:20424609 DOI:10.1038/sj.bjc.6605668]
285 Walter D,Satheesha S,Albrecht P,Bornhauser BC,D’Alessandro V,Oesch SM,Rehrauer H,Leuschner I,Koscielniak E,Gengler C,Moch H,Bernasconi M,Niggli FK,Sch?fer BW.CD133 positive embryonal rhabdomyosarcoma stem-like cell population is enriched in rhabdospheres.PLo S One 2011;6:e19506[PMID:21602936DOI:10.1371/journal.pone.0019506]
286 Civenni G,Malek A,Albino D,Garcia-Escudero R,Napoli S,Di Marco S,Pinton S,Sarti M,Carbone GM,Catapano CV.RNAi-mediated silencing of Myc transcription inhibits stem-like cell maintenance and tumorigenicity in prostate cancer.Cancer Res2013;73:6816-6827[PMID:24063893 DOI:10.1158/0008-5472.CAN-13-0615]
287 Akita H,Marquardt JU,Durkin ME,Kitade M,Seo D,Conner EA,Andersen JB,Factor VM,Thorgeirsson SS.MYC activates stem-like cell potential in hepatocarcinoma by a p53-dependent mechanism.Cancer Res 2014;74:5903-5913[PMID:25189530]
288 Hitchler MJ,Rice JC.Genome-wide epigenetic analysis of human pluripotent stem cells by Ch IP and Ch IP-Seq.Methods Mol Biol2011;767:253-267[PMID:21822881 DOI:10.1007/978-1-61779- 201 -4_19]
289 Revill K,Wang T,Lachenmayer A,Kojima K,Harrington A,Li J,Hoshida Y,Llovet JM,Powers S.Genome-wide methylation analysis and epigenetic unmasking identify tumor suppressor genes in hepatocellular carcinoma.Gastroenterology 2013;145:1424-35.e1-25[PMID:24012984 DOI:10.1053/j.gastro.2013.08.055]
290 Jurkowska RZ,Jurkowski TP,Jeltsch A.Structure and function of mammalian DNA methyltransferases.Chembiochem 2011;12:206 -222[PMID:21243710 DOI:10.1002/cbic.201000195]
291 Fatemi M,Hermann A,Gowher H,Jeltsch A.Dnmt3a and Dnmt1functionally cooperate during de novo methylation of DNA.Eur J Biochem 2002;269:4981-4984[PMID:12383256]
292 Walton EL,Francastel C,Velasco G.Maintenance of DNA methylation:Dnmt3b joins the dance.Epigenetics 2011;6:1373-1377[PMID:22048250 DOI:10.4161/epi.6.11.17978]
293 Jackson M,Krassowska A,Gilbert N,Chevassut T,Forrester L,Ansell J,Ramsahoye B.Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells.Mol Cell Biol 2004;24:8862-8871[PMID:15456861 DOI:10.1128/MCB.24.20.8862-8871.2004]
294 Zvetkova I,Apedaile A,Ramsahoye B,Mermoud JE,Crompton LA,John R,Feil R,Brockdorff N.Global hypomethylation of the genome in XX embryonic stem cells.Nat Genet 2005;37:1274-1279[PMID:16244654 DOI:10.1038/ng1663]
295 Fouse SD,Shen Y,Pellegrini M,Cole S,Meissner A,Van Neste L,Jaenisch R,Fan G.Promoter Cp G methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog,PcG complex,and histone H3 K4/K27 trimethylation.Cell Stem Cell 2008;2:160-169[PMID:18371437 DOI:10.1016/j.stem.2007.12.011]
296 Bibikova M,Chudin E,Wu B,Zhou L,Garcia EW,Liu Y,Shin S,Plaia TW,Auerbach JM,Arking DE,Gonzalez R,Crook J,Davidson B,Schulz TC,Robins A,Khanna A,Sartipy P,Hyllner J,Vanguri P,Savant-Bhonsale S,Smith AK,Chakravarti A,Maitra A,Rao M,Barker DL,Loring JF,Fan JB.Human embryonic stem cells have a unique epigenetic signature.Genome Res 2006;16:1075-1083[PMID:16899657 DOI:10.1101/gr.5319906]
297 Lister R,Pelizzola M,Dowen RH,Hawkins RD,Hon G,Tonti-Filippini J,Nery JR,Lee L,Ye Z,Ngo QM,Edsall L,Antosiewicz-Bourget J,Stewart R,Ruotti V,Millar AH,Thomson JA,Ren B,Ecker JR.Human DNA methylomes at base resolution show widespread epigenomic differences.Nature 2009;462:315-322[PMID:19829295 DOI:10.1038/nature08514]
298 Laurent L,Wong E,Li G,Huynh T,Tsirigos A,Ong CT,Low HM,Kin Sung KW,Rigoutsos I,Loring J,Wei CL.Dynamic changes in the human methylome during differentiation.Genome Res 2010;20 :320-331[PMID:20133333 DOI:10.1101/gr.101907.109]
299 Zhao L,Sun MA,Li Z,Bai X,Yu M,Wang M,Liang L,Shao X,Arnovitz S,Wang Q,He C,Lu X,Chen J,Xie H.The dynamics of DNA methylation fidelity during mouse embryonic stem cell selfrenewal and differentiation.Genome Res 2014;24:1296-1307[PMID:24835587 DOI:10.1101/gr.163147.113]
300 Arand J,Spieler D,Karius T,Branco MR,Meilinger D,Meissner A,Jenuwein T,Xu G,Leonhardt H,Wolf V,Walter J.In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases.PLoS Genet 2012;8:e1002750[PMID:22761581 DOI:10.1371/journal.pgen.1002750]
301 Ziller MJ,Müller F,Liao J,Zhang Y,Gu H,Bock C,Boyle P,Epstein CB,Bernstein BE,Lengauer T,Gnirke A,Meissner A.Genomic distribution and inter-sample variation of non-Cp G methylation across human cell types.PLo S Genet 2011;7:e1002389[PMID:22174693 DOI:10.1371/journal.pgen.1002389]
302 Li E,Bestor TH,Jaenisch R.Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.Cell 1992;69:915 -926[PMID:1606615]
303 Okano M,Bell DW,Haber DA,Li E.DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.Cell 1999;99:247-257[PMID:10555141]
304 Biniszkiewicz D,Gribnau J,Ramsahoye B,Gaudet F,Eggan K,Humpherys D,Mastrangelo MA,Jun Z,Walter J,Jaenisch R.Dnmt1 overexpression causes genomic hypermethylation,loss of imprinting,and embryonic lethality.Mol Cell Biol 2002;22:2124-2135[PMID:11884600]
305 Robertson KD,Uzvolgyi E,Liang G,Talmadge C,Sumegi J,Gonzales FA,Jones PA.The human DNA methyltransferases(DNMTs)1,3a and 3b:coordinate m RNA expression in normal tissues and overexpression in tumors.Nucleic Acids Res 1999;27:2291-2298[PMID:10325416]
306 Pawlak M,Jaenisch R.De novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells to a pluripotent state.Genes Dev 2011;25:1035-1040[PMID:21576263 DOI:10.1101/gad.2039011]
307 Tahiliani M,Koh KP,Shen Y,Pastor WA,Bandukwala H,Brudno Y,Agarwal S,Iyer LM,Liu DR,Aravind L,Rao A.Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1.Science 2009;324:930-935[PMID:19372391 DOI:10.1126/science.1170116]
308 Ito S,D’Alessio AC,Taranova OV,Hong K,Sowers LC,Zhang Y.Role of Tet proteins in 5mC to 5hmC conversion,ES-cell self-renewal and inner cell mass specification.Nature 2010;466:1129-1133[PMID:20639862 DOI:10.1038/nature09303]
309 He YF,Li BZ,Li Z,Liu P,Wang Y,Tang Q,Ding J,Jia Y,Chen Z,Li L,Sun Y,Li X,Dai Q,Song CX,Zhang K,He C,Xu GL.Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.Science 2011;333:1303-1307[PMID:21817016 DOI:10.1126/science.1210944]
310 Ito S,Shen L,Dai Q,Wu SC,Collins LB,Swenberg JA,He C,Zhang Y.Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5 -carboxylcytosine.Science 2011;333:1300-1303[PMID:21778364DOI:10.1126/science.1210597]
311 Globisch D,Münzel M,Müller M,Michalakis S,Wagner M,Koch S,Brückl T,Biel M,Carell T.Tissue distribution of 5 -hydroxymethylcytosine and search for active demethylation intermediates.PLoS One 2010;5:e15367[PMID:21203455 DOI:10 .1371/journal.pone.0015367]
312 Stroud H,Feng S,Morey Kinney S,Pradhan S,Jacobsen SE.5 -Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells.Genome Biol 2011;12:R54[PMID:21689397 DOI:10.1186/gb-2011-12-6-r54]
313 Ficz G,Branco MR,Seisenberger S,Santos F,Krueger F,Hore TA,Marques CJ,Andrews S,Reik W.Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation.Nature 2011;473:398-402[PMID:21460836 DOI:10 .1038/nature10008]
314 Robertson J,Robertson AB,Klungland A.The presence of 5 -hydroxymethylcytosine at the gene promoter and not in the gene body negatively regulates gene expression.Biochem Biophys Res Commun 2011;411:40-43[PMID:21703242 DOI:10.1016/j.bbrc.2011.06.077]
315 Koh KP,Yabuuchi A,Rao S,Huang Y,Cunniff K,Nardone J,Laiho A,Tahiliani M,Sommer CA,Mostoslavsky G,Lahesmaa R,Orkin SH,Rodig SJ,Daley GQ,Rao A.Tet1 and Tet2 regulate 5 -hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells.Cell Stem Cell 2011;8:200-213[PMID:21295276 DOI:10.1016/j.stem.2011.01.008]
316 Huang Y,Chavez L,Chang X,Wang X,Pastor WA,Kang J,Zepeda-Martínez JA,Pape UJ,Jacobsen SE,Peters B,Rao A.Distinct roles of the methylcytosine oxidases Tet1 and Tet2 in mouse embryonic stem cells.Proc Natl Acad Sci USA 2014;111:1361-1366[PMID:24474761 DOI:10.1073/pnas.1322921111]
317 Wu H,Zhang Y.Tet1 and 5-hydroxymethylation:a genome-wide view in mouse embryonic stem cells.Cell Cycle 2011;10:2428-2436[PMID:21750410]
318 Williams K,Christensen J,Pedersen MT,Johansen JV,Cloos PA,Rappsilber J,Helin K.TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.Nature 2011;473:343 -348[PMID:21490601 DOI:10.1038/nature10066]
319 Vella P,Scelfo A,Jammula S,Chiacchiera F,Williams K,Cuomo A,Roberto A,Christensen J,Bonaldi T,Helin K,Pasini D.Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells.Mol Cell 2013;49:645-656[PMID:23352454 DOI:10.1016/j.molcel.2012.12.019]
320 Shi FT,Kim H,Lu W,He Q,Liu D,Goodell MA,Wan M,Songyang Z.Ten-eleven translocation 1(Tet1)is regulated by O-linked N-acetylglucosamine transferase(Ogt)for target gene repression in mouse embryonic stem cells.J Biol Chem 2013;288:20776-20784[PMID:23729667 DOI:10.1074/jbc.M113.460386]
321 Freudenberg JM,Ghosh S,Lackford BL,Yellaboina S,Zheng X,Li R,Cuddapah S,Wade PA,Hu G,Jothi R.Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3signaling and results in loss of embryonic stem cell identity.Nucleic Acids Res 2012;40:3364-3377[PMID:22210859 DOI:10.1093/nar/gkr1253]
322 Dawlaty MM,Breiling A,Le T,Barrasa MI,Raddatz G,Gao Q,Powell BE,Cheng AW,Faull KF,Lyko F,Jaenisch R.Loss of Tet enzymes compromises proper differentiation of embryonic stem cells.Dev Cell 2014;29:102-111[PMID:24735881 DOI:10.1016/j.devcel.2014.03.003]
323 Dumitrescu RG,Verma M.Cancer epigenetics:Methods and protocols.Totowa NJ:Humana.London:Springer[distributor],2012
324 Esteller M.Epigenetics in cancer.N Engl J Med 2008;358:1148-1159[PMID:18337604 DOI:10.1056/NEJMra072067358/11/1148]
325 Feinberg AP,Ohlsson R,Henikoff S.The epigenetic progenitor origin of human cancer.Nat Rev Genet 2006;7:21-33[PMID:16369569]
326 Nishigaki M,Aoyagi K,Danjoh I,Fukaya M,Yanagihara K,Sakamoto H,Yoshida T,Sasaki H.Discovery of aberrant expression of R-RAS by cancer-linked DNA hypomethylation in gastric cancer using microarrays.Cancer Res 2005;65:2115-2124[PMID:15781621]
327 Nakamura M,Yonekawa Y,Kleihues P,Ohgaki H.Promoter hypermethylation of the RB1 gene in glioblastomas.Lab Invest2001;81:77-82[PMID:11204276]
328 Lahtz C,Pfeifer GP.Epigenetic changes of DNA repair genes in cancer.J Mol Cell Biol 2011;3:51-58[PMID:21278452 DOI:10 .1093/jmcb/mjq053]
329 Yasuda H,Soejima K,Watanabe H,Kawada I,Nakachi I,Yoda S,Nakayama S,Satomi R,Ikemura S,Terai H,Sato T,Suzuki S,Matsuzaki Y,Naoki K,Ishizaka A.Distinct epigenetic regulation of tumor suppressor genes in putative cancer stem cells of solid tumors.Int J Oncol 2010;37:1537-1546[PMID:21042723]
330 Ikegaki N,Shimada H,Fox AM,Regan PL,Jacobs JR,Hicks SL,Rappaport EF,Tang XX.Transient treatment with epigenetic modifiers yields stable neuroblastoma stem cells resembling aggressive large-cell neuroblastomas.Proc Natl Acad Sci USA 2013;110 :6097-6102[PMID:23479628 DOI:10.1073/pnas.1118262110]
331 Patra SK,Patra A,Zhao H,Dahiya R.DNA methyltransferase and demethylase in human prostate cancer.Mol Carcinog 2002;33:163 -171[PMID:11870882 DOI:10.1002/mc.10033]
332 Oh BK,Kim H,Park HJ,Shim YH,Choi J,Park C,Park YN.DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation.Int J Mol Med 2007;20:65-73[PMID:17549390]
333 Melki JR,Warnecke P,Vincent PC,Clark SJ.Increased DNA methyltransferase expression in leukaemia.Leukemia 1998;12:311 -316[PMID:9529124]
334 Wu J,Issa JP,Herman J,Bassett DE,Nelkin BD,Baylin SB.Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH 3T3 cells.Proc Natl Acad Sci USA 1993;90:8891-8895[PMID:8415627]
335 MacL eod AR,Szyf M.Expression of antisense to DNA methylt-ransferase m RNA induces DNA demethylation and inhibits tumorigenesis.J Biol Chem 1995;270:8037-8043[PMID:7713905]
336 Morita R,Hirohashi Y,Suzuki H,Takahashi A,Tamura Y,Kanaseki T,Asanuma H,Inoda S,Kondo T,Hashino S,Hasegawa T,Tokino T,Toyota M,Asaka M,Torigoe T,Sato N.DNA methyltransferase 1is essential for initiation of the colon cancers.Exp Mol Pathol 2013;94 :322-329[PMID:23064049 DOI:10.1016/j.yexmp.2012.10.004]
337 Trowbridge JJ,Sinha AU,Zhu N,Li M,Armstrong SA,Orkin SH.Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through derepression of bivalent chromatin domains.Genes Dev 2012;26:344-349[PMID:22345515 DOI:10.1101/gad.184341.111]
338 Choi DS,Blanco E,Kim YS,Rodriguez AA,Zhao H,Huang TH,Chen CL,Jin G,Landis MD,Burey LA,Qian W,Granados SM,Dave B,Wong HH,Ferrari M,Wong ST,Chang JC.Chloroquine eliminates cancer stem cells through deregulation of Jak2 and DNMT1.Stem Cells 2014;32:2309-2323[PMID:24809620 DOI:10 .1002/stem.1746]
339 Mariani CJ,Madzo J,Moen EL,Yesilkanal A,Godley LA.Alterations of 5-hydroxymethylcytosine in human cancers.Cancers(Basel)2013;5:786-814[PMID:24202321 DOI:10.3390/cancers5030786]
340 Lorsbach RB,Moore J,Mathew S,Raimondi SC,Mukatira ST,Downing JR.TET1,a member of a novel protein family,is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23).Leukemia 2003;17:637-641[PMID:12646957 DOI:10.1038/sj.leu.2402834]
341 Ono R,Taki T,Taketani T,Taniwaki M,Kobayashi H,Hayashi Y.LCX,leukemia-associated protein with a CXXC domain,is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23).Cancer Res 2002;62:4075-4080[PMID:12124344]
342 Abdel-Wahab O,Mullally A,Hedvat C,Garcia-Manero G,Patel J,Wadleigh M,Malinge S,Yao J,Kilpivaara O,Bhat R,Huberman K,Thomas S,Dolgalev I,Heguy A,Paietta E,Le Beau MM,Beran M,Tallman MS,Ebert BL,Kantarjian HM,Stone RM,Gilliland DG,Crispino JD,Levine RL.Genetic characterization of TET1,TET2,and TET3 alterations in myeloid malignancies.Blood 2009;114:144 -147[PMID:19420352 DOI:10.1182/blood-2009-03-210039]
343 Tsai YP,Chen HF,Chen SY,Cheng WC,Wang HW,Shen ZJ,Song C,Teng SC,He C,Wu KJ.TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator.Genome Biol 2014;15:513[PMID:25517638 DOI:10.1186/s13059-014-0513-0]
344 Song SJ,Poliseno L,Song MS,Ala U,Webster K,Ng C,Beringer G,Brikbak NJ,Yuan X,Cantley LC,Richardson AL,Pandolfi PP.Micro RNA-antagonism regulates breast cancer stemness and metastasis via TET-family-dependent chromatin remodeling.Cell 2013;154:311-324[PMID:23830207 DOI:10.1016/j.cell.2013.06.026]
345 Plimack ER,Stewart DJ,Issa JP.Combining epigenetic and cytotoxic therapy in the treatment of solid tumors.J Clin Oncol 2007;25:4519-4521[PMID:17925545 DOI:10.1200/JCO.2007.12.6029]
346 Cortez CC,Jones PA.Chromatin,cancer and drug therapies.Mutat Res 2008;647:44-51[PMID:18691602 DOI:10.1016/j.mrfmmm.2008.07.006]
347 Cedar H,Bergman Y.Linking DNA methylation and histone modification:patterns and paradigms.Nat Rev Genet 2009;10:295 -304[PMID:19308066]
348 Haberland M,Montgomery RL,Olson EN.The many roles of histone deacetylases in development and physiology:implications for disease and therapy.Nat Rev Genet 2009;10:32-42[PMID:19065135 DOI:10.1038/nrg2485]
349 Shi Y,Whetstine JR.Dynamic regulation of histone lysine methylation by demethylases.Mol Cell 2007;25:1-14[PMID:17218267 DOI:10.1016/j.molcel.2006.12.010]
350 Azuara V,Perry P,Sauer S,Spivakov M,J?rgensen HF,John RM,Gouti M,Casanova M,Warnes G,Merkenschlager M,Fisher AG.Chromatin signatures of pluripotent cell lines.Nat Cell Biol 2006;8:532 -538[PMID:16570078 DOI:10.1038/ncb1403]
351 Meshorer E,Misteli T.Chromatin in pluripotent embryonic stem cells and differentiation.Nat Rev Mol Cell Biol 2006;7:540-546[PMID:16723974 DOI:10.1038/nrm1938]
352 Bernstein BE,Mikkelsen TS,Xie X,Kamal M,Huebert DJ,Cuff J,Fry B,Meissner A,Wernig M,Plath K,Jaenisch R,Wagschal A,Feil R,Schreiber SL,Lander ES.A bivalent chromatin structure marks key developmental genes in embryonic stem cells.Cell 2006;125 :315-326[PMID:16630819 DOI:10.1016/j.cell.2006.02.041]
353 Voigt P,Tee WW,Reinberg D.A double take on bivalent promoters.Genes Dev 2013;27:1318-1338[PMID:23788621 DOI:10.1101/gad.219626.113]
354 Denissov S,Hofemeister H,Marks H,Kranz A,Ciotta G,Singh S,Anastassiadis K,Stunnenberg HG,Stewart AF.Mll2 is required for H3K4 trimethylation on bivalent promoters in embryonic stem cells,whereas Mll1 is redundant.Development 2014;141:526-537[PMID:24423662 DOI:10.1242/dev.102681]
355 Margueron R,Reinberg D.The Polycomb complex PRC2 and its mark in life.Nature 2011;469:343-349[PMID:21248841 DOI:10 .1038/nature09784]
356 Young MD,Willson TA,Wakefield MJ,Trounson E,Hilton DJ,Blewitt ME,Oshlack A,Majewski IJ.Ch IP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity.Nucleic Acids Res 2011;39:7415-7427[PMID:21652639DOI:10.1093/nar/gkr416]
357 Laugesen A,Helin K.Chromatin repressive complexes in stem cells,development,and cancer.Cell Stem Cell 2014;14:735-751[PMID:24905164 DOI:10.1016/j.stem.2014.05.006]
358 Gil J,O’Loghlen A.PRC1 complex diversity:where is it taking us?Trends Cell Biol 2014;24:632-641[PMID:25065329 DOI:10 .1016/j.tcb.2014.06.005]
359 Faust C,Schumacher A,Holdener B,Magnuson T.The eed mutation disrupts anterior mesoderm production in mice.Development 1995;121:273-285[PMID:7768172]
360 Chamberlain SJ,Yee D,Magnuson T.Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency.Stem Cells 2008;26:1496-1505[PMID:18403752DOI:10.1634/stemcells.2008-0102]
361 Montgomery ND,Yee D,Chen A,Kalantry S,Chamberlain SJ,Otte AP,Magnuson T.The murine polycomb group protein Eed is required for global histone H3 lysine-27 methylation.Curr Biol 2005;15:942-947[PMID:15916951 DOI:10.1016/j.cub.2005.04.051]
362 Pasini D,Bracken AP,Hansen JB,Capillo M,Helin K.The polycomb group protein Suz12 is required for embryonic stem cell differentiation.Mol Cell Biol 2007;27:3769-3779[PMID:17339329 DOI:10.1128/MCB.01432-06]
363 Shen X,Liu Y,Hsu YJ,Fujiwara Y,Kim J,Mao X,Yuan GC,Orkin SH.EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency.Mol Cell 2008;32:491-502[PMID:19026780 DOI:10 .1016/j.molcel.2008.10.016]
364 Akasaka T,van Lohuizen M,van der Lugt N,Mizutani-Koseki Y,Kanno M,Taniguchi M,Vidal M,Alkema M,Berns A,Koseki H.Mice doubly deficient for the Polycomb Group genes Mel18and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression.Development 2001;128:1587-1597[PMID:11290297]
365 Leeb M,Wutz A.Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells.J Cell Biol 2007;178:219-229[PMID:17620408 DOI:10.1083/jcb.200612127]
366 Endoh M,Endo TA,Endoh T,Fujimura Y,Ohara O,Toyoda T,Otte AP,Okano M,Brockdorff N,Vidal M,Koseki H.Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity.Development 2008;135 :1513-1524[PMID:18339675 DOI:10.1242/dev.014340]
367 Aloia L,Di Stefano B,Di Croce L.Polycomb complexes in stem cells and embryonic development.Development 2013;140:2525-2534[PMID:23715546 DOI:10.1242/dev.091553]
368 Ku M,Koche RP,Rheinbay E,Mendenhall EM,Endoh M,Mikkelsen TS,Presser A,Nusbaum C,Xie X,Chi AS,Adli M,Kasif S,Ptaszek LM,Cowan CA,Lander ES,Koseki H,Bernstein BE.Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains.PLo S Genet 2008;4:e1000242[PMID:18974828 DOI:10.1371/journal.pgen.1000242]
369 Schuettengruber B,Chourrout D,Vervoort M,Leblanc B,Cavalli G.Genome regulation by polycomb and trithorax proteins.Cell 2007;128 :735-745[PMID:17320510 DOI:10.1016/j.cell.2007.02.009]
370 Schuettengruber B,Martinez AM,Iovino N,Cavalli G.Trithorax group proteins:switching genes on and keeping them active.Nat Rev Mol Cell Biol 2011;12:799-814[PMID:22108599 DOI:10 .1038/nrm3230]
371 Whetstine JR,Nottke A,Lan F,Huarte M,Smolikov S,Chen Z,Spooner E,Li E,Zhang G,Colaiacovo M,Shi Y.Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases.Cell 2006;125:467-481[PMID:16603238 DOI:10 .1016/j.cell.2006.03.028]
372 Loh YH,Zhang W,Chen X,George J,Ng HH.Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells.Genes Dev 2007;21:2545-2557[PMID:17938240DOI:10.1101/gad.1588207]
373 Whyte WA,Bilodeau S,Orlando DA,Hoke HA,Frampton GM,Foster CT,Cowley SM,Young RA.Enhancer decommissioning by LSD1 during embryonic stem cell differentiation.Nature 2012;482:221 -225[PMID:22297846 DOI:10.1038/nature10805]
374 Tachibana M,Sugimoto K,Fukushima T,Shinkai Y.Set domain-containing protein,G9a,is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3.J Biol Chem 2001;276:25309-25317[PMID:11316813 DOI:10.1074/jbc.M101914200]
375 Lee KK,Workman JL.Histone acetyltransferase complexes:one size doesn’t fit all.Nat Rev Mol Cell Biol 2007;8:284-295[PMID:17380162 DOI:10.1038/nrm2145]
376 Wang Z,Zang C,Cui K,Schones DE,Barski A,Peng W,Zhao K.Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes.Cell 2009;138:1019-1031[PMID:19698979 DOI:10.1016/j.cell.2009.06.049]
377 Dovey OM,Foster CT,Cowley SM.Histone deacetylase 1(HDAC1),but not HDAC2,controls embryonic stem cell differentiation.Proc Natl Acad Sci USA 2010;107:8242-8247[PMID:20404188 DOI:10 .1073/pnas.1000478107]
378 Kelly RD,Cowley SM.The physiological roles of histone deacetylase(HDAC)1 and 2:complex co-stars with multiple leading parts.Biochem Soc Trans 2013;41:741-749[PMID:23697933 DOI:10.1042/BST20130010]
379 Kretsovali A,Hadjimichael C,Charmpilas N.Histone deacetylase inhibitors in cell pluripotency,differentiation,and reprogramming.Stem Cells Int 2012;2012:184154[PMID:22550500 DOI:10 .1155/2012/184154]
380 Huangfu D,Maehr R,Guo W,Eijkelenboom A,Snitow M,Chen AE,Melton DA.Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds.Nat Biotechnol 2008;26:795-797[PMID:18568017 DOI:10.1038/nbt1418]
381 Hayakawa T,Nakayama J.Physiological roles of class I HDAC complex and histone demethylase.J Biomed Biotechnol 2011;2011:129383[PMID:21049000 DOI:10.1155/2011/129383]
382 Reynolds N,Latos P,Hynes-Allen A,Loos R,Leaford D,O’Shaughnessy A,Mosaku O,Signolet J,Brennecke P,Kalkan T,Costello I,Humphreys P,Mansfield W,Nakagawa K,Strouboulis J,Behrens A,Bertone P,Hendrich B.NuR D suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment.Cell Stem Cell 2012;10:583-594[PMID:22560079 DOI:10.1016/j.stem.2012.02.020]
383 Buganim Y,Faddah DA,Cheng AW,Itskovich E,Markoulaki S,Ganz K,Klemm SL,van Oudenaarden A,Jaenisch R.Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase.Cell 2012;150:1209-1222[PMID:22980981 DOI:10.1016/j.cell.2012.08.023]
384 Luo M,Ling T,Xie W,Sun H,Zhou Y,Zhu Q,Shen M,Zong L,Lyu G,Zhao Y,Ye T,Gu J,Tao W,Lu Z,Grummt I.NuR D blocks reprogramming of mouse somatic cells into pluripotent stem cells.Stem Cells 2013;31:1278-1286[PMID:23533168 DOI:10.1002/stem.1374]
385 Yu C,Liu K,Tang S,Ding S.Chemical approaches to cell reprogramming.Curr Opin Genet Dev 2014;28:50-56[PMID:25461450 DOI:10.1016/j.gde.2014.09.006]
386 Fraga MF,Ballestar E,Paz MF,Ropero S,Setien F,Ballestar ML,Heine-Su?er D,Cigudosa JC,Urioste M,Benitez J,Boix-Chornet M,Sanchez-Aguilera A,Ling C,Carlsson E,Poulsen P,Vaag A,Stephan Z,Spector TD,Wu YZ,Plass C,Esteller M.Epigenetic differences arise during the lifetime of monozygotic twins.Proc Natl Acad Sci USA 2005;102:10604-10609[PMID:16009939DOI:10.1073/pnas.0500398102]
387 Seligson DB,Horvath S,Shi T,Yu H,Tze S,Grunstein M,Kurdistani SK.Global histone modification patterns predict risk of prostate cancer recurrence.Nature 2005;435:1262-1266[PMID:15988529 DOI:10.1038/nature03672]
388 Li G,Warden C,Zou Z,Neman J,Krueger JS,Jain A,Jandial R,Chen M.Altered expression of polycomb group genes in glioblastoma multiforme.PLo S One 2013;8:e80970[PMID:24260522 DOI:10.1371/journal.pone.0080970]
389 Valk-Lingbeek ME,Bruggeman SW,van Lohuizen M.Stem cells and cancer;the polycomb connection.Cell 2004;118:409-418[PMID:15315754 DOI:10.1016/j.cell.2004.08.005]
390 Schulte JH,Lim S,Schramm A,Friedrichs N,Koster J,Versteeg R,Ora I,Pajtler K,Klein-Hitpass L,Kuhfittig-Kulle S,Metzger E,Schüle R,Eggert A,Buettner R,Kirfel J.Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma:implications for therapy.Cancer Res 2009;69 :2065-2071[PMID:19223552 DOI:10.1158/0008-5472.CAN-08-1735]
391 Halkidou K,Gaughan L,Cook S,Leung HY,Neal DE,Robson CN.Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer.Prostate 2004;59:177-189[PMID:15042618 DOI:10.1002/pros.20022]
392 Carew JS,Giles FJ,Nawrocki ST.Histone deacetylase inhibitors:mechanisms of cell death and promise in combination cancer therapy.Cancer Lett 2008;269:7-17[PMID:18462867 DOI:10 .1016/j.canlet.2008.03.037]
393 van Vlerken LE,Kiefer CM,Morehouse C,Li Y,Groves C,Wilson SD,Yao Y,Hollingsworth RE,Hurt EM.EZH2 is required for breast and pancreatic cancer stem cell maintenance and can be used as a functional cancer stem cell reporter.Stem Cells Transl Med2013;2:43-52[PMID:23283488 DOI:10.5966/sctm.2012-0036]
394 Iliopoulos D,Hirsch HA,Wang G,Struhl K.Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion.Proc Natl Acad Sci USA 2011;108:1397-1402[PMID:21220315 DOI:10.1073/pnas.1018898108]
395 SuvàML,Riggi N,Janiszewska M,Radovanovic I,Provero P,Stehle JC,Baumer K,Le Bitoux MA,Marino D,Cironi L,Marquez VE,Clément V,Stamenkovic I.EZH2 is essential for glioblastoma cancer stem cell maintenance.Cancer Res 2009;69:9211-9218[PMID:19934320 DOI:10.1158/0008-5472.CAN-09-1622]
396 Crea F,Duhagon MA,Farrar WL,Danesi R.Pharmacogenomics and cancer stem cells:a changing landscape?Trends Pharmacol Sci 2011;32:487-494[PMID:21529973 DOI:10.1016/j.tips.2011.03.010]
397 Richter GH,Plehm S,Fasan A,R?ssler S,Unland R,Bennani-Baiti IM,Hotfilder M,L?wel D,von Luettichau I,Mossbrugger I,Quintanilla-Martinez L,Kovar H,Staege MS,Müller-Tidow C,Burdach S.EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation.Proc Natl Acad Sci USA 2009;106:5324-5329[PMID:19289832 DOI:10.1073/pnas.0810759106]
398 Gupta PB,Fillmore CM,Jiang G,Shapira SD,Tao K,Kuperwasser C,Lander ES.Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells.Cell 2011;146:633-644[PMID:21854987 DOI:10.1016/j.cell.2011.07.026]
399 Chang B,Li S,He Q,Liu Z,Zhao L,Zhao T,Wang A.Deregulation of Bmi-1 is associated with enhanced migration,invasion and poor prognosis in salivary adenoid cystic carcinoma.Biochim Biophys Acta 2014;1840:3285-3291[PMID:25151043 DOI:10.1016/j.bbagen.2014.08.005]
400 Jin J,Lv X,Chen L,Zhang W,Li J,Wang Q,Wang R,Lu X,Miao D.Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance.Aging Cell2014;13:797-809[PMID:24915841 DOI:10.1111/acel.12236]
401 Yu X,Jiang X,Li H,Guo L,Jiang W,Lu SH.miR-203 inhibits the proliferation and self-renewal of esophageal cancer stem-like cells by suppressing stem renewal factor Bmi-1.Stem Cells Dev 2014;23 :576-585[PMID:24219349 DOI:10.1089/scd.2013.0308]
402 N?r C,Zhang Z,Warner KA,Bernardi L,Visioli F,Helman JI,Roesler R,N?r JE.Cisplatin induces Bmi-1 and enhances the stem cell fraction in head and neck cancer.Neoplasia 2014;16:137-146[PMID:24709421 DOI:10.1593/neo.131744]
403 Liu XF,Yang WT,Xu R,Liu JT,Zheng PS.Cervical cancer cells with positive Sox2 expression exhibit the properties of cancer stem cells.PLoS One 2014;9:e87092[PMID:24489842 DOI:10.1371/journal.pone.0087092]
404 Kreso A,van Galen P,Pedley NM,Lima-Fernandes E,Frelin C,Davis T,Cao L,Baiazitov R,Du W,Sydorenko N,Moon YC,Gibson L,Wang Y,Leung C,Iscove NN,Arrowsmith CH,Szentgyorgyi E,Gallinger S,Dick JE,O’Brien CA.Self-renewal as a therapeutic target in human colorectal cancer.Nat Med 2014;20:29 -36[PMID:24292392 DOI:10.1038/nm.3418]
405 Yu D,Liu Y,Yang J,Jin C,Zhao X,Cheng J,Liu X,Qi X.Clinical implications of BMI-1 in cancer stem cells of laryngeal carcinoma.Cell Biochem Biophys 2015;71:261-269[PMID:25241082 DOI:10 .1007/s12013-014-0194-z]
406 Zhang S,Cui B,Lai H,Liu G,Ghia EM,Widhopf GF,Zhang Z,Wu CC,Chen L,Wu R,Schwab R,Carson DA,Kipps TJ.Ovarian cancer stem cells express ROR1,which can be targeted for anti-cancer-stem-cell therapy.Proc Natl Acad Sci USA 2014;111:17266-17271[PMID:25411317 DOI:10.1073/pnas.1419599111]
407 Iliopoulos D,Lindahl-Allen M,Polytarchou C,Hirsch HA,Tsichlis PN,Struhl K.Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells.Mol Cell 2010;39:761-772[PMID:20832727 DOI:10.1016/j.molcel.2010.08.013]
408 Benoit YD,Witherspoon MS,Laursen KB,Guezguez A,Beauséjour M,Beaulieu JF,Lipkin SM,Gudas LJ.Pharmacological inhibition of polycomb repressive complex-2 activity induces apoptosis in human colon cancer stem cells.Exp Cell Res 2013;319:1463-1470[PMID:23588203 DOI:10.1016/j.yexcr.2013.04.006]
409 Heddleston JM,Wu Q,Rivera M,Minhas S,Lathia JD,Sloan AE,Iliopoulos O,Hjelmeland AB,Rich JN.Hypoxia-induced mixed-lineage leukemia 1 regulates glioma stem cell tumorigenic potential.Cell Death Differ 2012;19:428-439[PMID:21836617 DOI:10 .1038/cdd.2011.109]
410 Wang J,Lu F,Ren Q,Sun H,Xu Z,Lan R,Liu Y,Ward D,Quan J,Ye T,Zhang H.Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem cell properties.Cancer Res 2011;71:7238-7249[PMID:21975933 DOI:10 .1158/0008-5472.CAN-11-0896]
411 Giudice FS,Pinto DS,N?r JE,Squarize CH,Castilho RM.Inhibition of histone deacetylase impacts cancer stem cells and induces epithelial-mesenchyme transition of head and neck cancer.PLo S One 2013;8:e58672[PMID:23527004 DOI:10.1371/journal.pone.0058672]
412 Bernstein E,Kim SY,Carmell MA,Murchison EP,Alcorn H,Li MZ,Mills AA,Elledge SJ,Anderson KV,Hannon GJ.Dicer is essential for mouse development.Nat Genet 2003;35:215-217[PMID:14528307 DOI:10.1038/ng1253]
413 Wang Y,Medvid R,Melton C,Jaenisch R,Blelloch R.DGCR8 is essential for microR NA biogenesis and silencing of embryonic stem cell self-renewal.Nat Genet 2007;39:380-385[PMID:17259983DOI:10.1038/ng1969]
414 Marson A,Levine SS,Cole MF,Frampton GM,Brambrink T,Johnstone S,Guenther MG,Johnston WK,Wernig M,Newman J,Calabrese JM,Dennis LM,Volkert TL,Gupta S,Love J,Hannett N,Sharp PA,Bartel DP,Jaenisch R,Young RA.Connecting microR NA genes to the core transcriptional regulatory circuitry of embryonic stem cells.Cell 2008;134:521-533[PMID:18692474DOI:10.1016/j.cell.2008.07.020]
415 Babiarz JE,Ruby JG,Wang Y,Bartel DP,Blelloch R.Mouse ES cells express endogenous sh RNAs,si RNAs,and other Microprocessor-independent,Dicer-dependent small RNAs.Genes Dev 2008;22:2773-2785[PMID:18923076 DOI:10.1101/gad.1705308]
416 Sinkkonen L,Hugenschmidt T,Berninger P,Gaidatzis D,Mohn F,Artus-Revel CG,Zavolan M,Svoboda P,Filipowicz W.MicroR NAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells.Nat Struct Mol Biol 2008;15:259-267[PMID:18311153 DOI:10 .1038/nsmb.1391]
417 Benetti R,Gonzalo S,Jaco I,Mu?oz P,Gonzalez S,Schoeftner S,Murchison E,Andl T,Chen T,Klatt P,Li E,Serrano M,Millar S,Hannon G,Blasco MA.A mammalian microR NA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases.Nat Struct Mol Biol 2008;15 :268-279[PMID:18311151 DOI:10.1038/nsmb.1399]
418 Wang Y,Xu Z,Jiang J,Xu C,Kang J,Xiao L,Wu M,Xiong J,Guo X,Liu H.Endogenous mi RNA sponge linc RNA-Ro R regulates Oct4,Nanog,and Sox2 in human embryonic stem cell self-renewal.Dev Cell 2013;25:69-80[PMID:23541921 DOI:10 .1016/j.devcel.2013.03.002]
419 Wang Y,Baskerville S,Shenoy A,Babiarz JE,Baehner L,Blelloch R.Embryonic stem cell-specific micro RNAs regulate the G1-S transition and promote rapid proliferation.Nat Genet 2008;40:1478-1483[PMID:18978791 DOI:10.1038/ng.250]
420 Qi J,Yu JY,Shcherbata HR,Mathieu J,Wang AJ,Seal S,Zhou W,Stadler BM,Bourgin D,Wang L,Nelson A,Ware C,Raymond C,Lim LP,Magnus J,Ivanovska I,Diaz R,Ball A,Cleary MA,Ruohola-Baker H.microR NAs regulate human embryonic stem cell division.Cell Cycle 2009;8:3729-3741[PMID:19823043]
421 Sengupta S,Nie J,Wagner RJ,Yang C,Stewart R,Thomson JA.MicroR NA 92b controls the G1/S checkpoint gene p57 in human embryonic stem cells.Stem Cells 2009;27:1524-1528[PMID:19544458 DOI:10.1002/stem.84]
422 Tay YM,Tam WL,Ang YS,Gaughwin PM,Yang H,Wang W,Liu R,George J,Ng HH,Perera RJ,Lufkin T,Rigoutsos I,Thomson AM,Lim B.Micro RNA-134 modulates the differentiation of mouse embryonic stem cells,where it causes post-transcriptional attenuation of Nanog and LRH1.Stem Cells 2008;26:17-29[PMID:17916804 DOI:10.1634/stemcells.2007-0295]
423 Tay Y,Zhang J,Thomson AM,Lim B,Rigoutsos I.MicroR NAs to Nanog,Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation.Nature 2008;455:1124-1128[PMID:18806776DOI:10.1038/nature07299]
424 Xu N,Papagiannakopoulos T,Pan G,Thomson JA,Kosik KS.MicroR NA-145 regulates OCT4,SOX2,and KLF4 and represses pluripotency in human embryonic stem cells.Cell 2009;137:647 -658[PMID:19409607 DOI:10.1016/j.cell.2009.02.038]
425 Singh SK,Kagalwala MN,Parker-Thornburg J,Adams H,Majumder S.REST maintains self-renewal and pluripotency of embryonic stem cells.Nature 2008;453:223-227[PMID:18362916 DOI:10.1038/nature06863]
426 Gangaraju VK,Lin H.MicroR NAs:key regulators of stem cells.Nat Rev Mol Cell Biol 2009;10:116-125[PMID:19165214 DOI:10 .1038/nrm2621]
427 Landgraf P,Rusu M,Sheridan R,Sewer A,Iovino N,Aravin A,Pfeffer S,Rice A,Kamphorst AO,Landthaler M,Lin C,Socci ND,Hermida L,Fulci V,Chiaretti S,FoàR,Schliwka J,Fuchs U,Novosel A,Müller RU,Schermer B,Bissels U,Inman J,Phan Q,Chien M,Weir DB,Choksi R,De Vita G,Frezzetti D,Trompeter HI,Hornung V,Teng G,Hartmann G,Palkovits M,Di Lauro R,Wernet P,Macino G,Rogler CE,Nagle JW,Ju J,Papavasiliou FN,Benzing T,Lichter P,Tam W,Brownstein MJ,Bosio A,Borkhardt A,Russo JJ,Sander C,Zavolan M,Tuschl T.A mammalian microR NA expression atlas based on small RNA library sequencing.Cell 2007;129:1401-1414[PMID:17604727 DOI:10.1016/j.cell.2007.04.040]
428 O’Loghlen A,Mu?oz-Cabello AM,Gaspar-Maia A,Wu HA,Banito A,Kunowska N,Racek T,Pemberton HN,Beolchi P,Lavial F,Masui O,Vermeulen M,Carroll T,Graumann J,Heard E,Dillon N,Azuara V,Snijders AP,Peters G,Bernstein E,Gil J.MicroR NA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation.Cell Stem Cell 2012;10:33-46[PMID:22226354 DOI:10.1016/j.stem.2011.12.004]
429 Tarantino C,Paolella G,Cozzuto L,Minopoli G,Pastore L,Parisi S,Russo T.miR NA 34a,100,and 137 modulate differentiation of mouse embryonic stem cells.FASEB J 2010;24:3255-3263[PMID:20439489 DOI:10.1096/fj.09-152207]
430 Melton C,Judson RL,Blelloch R.Opposing microR NA families regulate self-renewal in mouse embryonic stem cells.Nature 2010;463 :621-626[PMID:20054295 DOI:10.1038/nature08725]
431 Viswanathan SR,Daley GQ,Gregory RI.Selective blockade of microR NA processing by Lin28.Science 2008;320:97-100[PMID:18292307 DOI:10.1126/science.1154040]
432 Newman MA,Thomson JM,Hammond SM.Lin-28 interaction with the Let-7 precursor loop mediates regulated micro RNA processing.RNA 2008;14:1539-1549[PMID:18566191 DOI:10 .1261/rna.1155108]
433 Huang TH,Esteller M.Chromatin remodeling in mammary gland differentiation and breast tumorigenesis.Cold Spring Harb Perspect Biol 2010;2:a004515[PMID:20610549 DOI:10.1101/cshperspect.a004515]
434 Yu F,Yao H,Zhu P,Zhang X,Pan Q,Gong C,Huang Y,Hu X,Su F,Lieberman J,Song E.let-7 regulates self renewal and tumorigenicity of breast cancer cells.Cell 2007;131:1109-1123[PMID:18083101 DOI:10.1016/j.cell.2007.10.054]
435 Yu F,Deng H,Yao H,Liu Q,Su F,Song E.Mir-30 reduction maintains self-renewal and inhibits apoptosis in breast tumor-initiating cells.Oncogene 2010;29:4194-4204[PMID:20498642DOI:10.1038/onc.2010.167]
436 Iliopoulos D,Hirsch HA,Struhl K.An epigenetic switch involving NF-kappaB,Lin28,Let-7 MicroR NA,and IL6 links inflammation to cell transformation.Cell 2009;139:693-706[PMID:19878981DOI:10.1016/j.cell.2009.10.014]
437 Shimono Y,Zabala M,Cho RW,Lobo N,Dalerba P,Qian D,Diehn M,Liu H,Panula SP,Chiao E,Dirbas FM,Somlo G,Pera RA,Lao K,Clarke MF.Downregulation of miR NA-200c links breast cancer stem cells with normal stem cells.Cell 2009;138:592-603[PMID:19665978 DOI:10.1016/j.cell.2009.07.011]
438 Gregory PA,Bracken CP,Bert AG,Goodall GJ.Micro RNAs as regulators of epithelial-mesenchymal transition.Cell Cycle 2008;7:3112-3118[PMID:18927505]
439 Park SM,Gaur AB,Lengyel E,Peter ME.The mi R-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.Genes Dev 2008;22:894 -907[PMID:18381893 DOI:10.1101/gad.1640608]
440 Polytarchou C,Iliopoulos D,Struhl K.An integrated trans-criptional regulatory circuit that reinforces the breast cancer stem cell state.Proc Natl Acad Sci USA 2012;109:14470-14475[PMID:22908280 DOI:10.1073/pnas.1212811109]
441 Schraivogel D,Weinmann L,Beier D,Tabatabai G,Eichner A,Zhu JY,Anton M,Sixt M,Weller M,Beier CP,Meister G.CAMTA1 is a novel tumour suppressor regulated by miR-9/9*in glioblastoma stem cells.EMBO J 2011;30:4309-4322[PMID:21857646 DOI:10 .1038/emboj.2011.301]
442 Godlewski J,Nowicki MO,Bronisz A,Williams S,Otsuki A,Nuovo G,Raychaudhury A,Newton HB,Chiocca EA,Lawler S.Targeting of the Bmi-1 oncogene/stem cell renewal factor by microR NA-128inhibits glioma proliferation and self-renewal.Cancer Res 2008;68 :9125-9130[PMID:19010882 DOI:10.1158/0008-5472.CAN-08-2629]
443 Molofsky AV,Pardal R,Iwashita T,Park IK,Clarke MF,Morrison SJ.Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation.Nature 2003;425:962-967[PMID:14574365 DOI:10.1038/nature02060]
444 Li Y,Guessous F,Zhang Y,Dipierro C,Kefas B,Johnson E,Marcinkiewicz L,Jiang J,Yang Y,Schmittgen TD,Lopes B,Schiff D,Purow B,Abounader R.Micro RNA-34a inhibits glioblastoma growth by targeting multiple oncogenes.Cancer Res 2009;69 :7569-7576[PMID:19773441 DOI:10.1158/0008-5472.CAN-09-0529]
445 Yang YP,Chien Y,Chiou GY,Cherng JY,Wang ML,Lo WL,Chang YL,Huang PI,Chen YW,Shih YH,Chen MT,Chiou SH.Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microR NA145 with cationic polyurethane-short branch PEI.Biomaterials 2012;33:1462-1476[PMID:22098779DOI:10.1016/j.biomaterials.2011.10.071]
446 Gal H,Pandi G,Kanner AA,Ram Z,Lithwick-Yanai G,Amariglio N,Rechavi G,Givol D.MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cells.Biochem Biophys Res Commun 2008;376:86-90[PMID:18765229 DOI:10.1016/j.bbrc.2008.08.107]
447 Garzia L,Andolfo I,Cusanelli E,Marino N,Petrosino G,De Martino D,Esposito V,Galeone A,Navas L,Esposito S,Gargiulo S,Fattet S,Donofrio V,Cinalli G,Brunetti A,Vecchio LD,Northcott PA,Delattre O,Taylor MD,Iolascon A,Zollo M.MicroR NA-199b- 5 p impairs cancer stem cells through negative regulation of HES1in medulloblastoma.PLoS One 2009;4:e4998[PMID:19308264DOI:10.1371/journal.pone.0004998]
448 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]
449 Hsieh IS,Chang KC,Tsai YT,Ke JY,Lu PJ,Lee KH,Yeh SD,Hong TM,Chen YL.MicroR NA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway.Carcinogenesis 2013;34:530-538[PMID:23188675 DOI:10.1093/carcin/bgs371]
450 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.MicroR NA mi R-34 inhibits human pancreatic cancer tumor-initiating cells.PLoS One 2009;4:e6816[PMID:19714243 DOI:10.1371/journal.pone.0006816]
451 Ji Q,Hao X,Meng Y,Zhang M,Desano J,Fan D,Xu L.Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres.BMC Cancer 2008;8:266[PMID:18803879 DOI:10.1186/1471-2407-8-266]
452 Bu P,Chen KY,Chen JH,Wang L,Walters J,Shin YJ,Goerger JP,Sun J,Witherspoon M,Rakhilin N,Li J,Yang H,Milsom J,Lee S,Zipfel W,Jin MM,Gümü?ZH,Lipkin SM,Shen X.A microR NA mi R-34a-regulated bimodal switch targets Notch in colon cancer stem cells.Cell Stem Cell 2013;12:602-615[PMID:23642368DOI:10.1016/j.stem.2013.03.002]
453 Sheik Mohamed J,Gaughwin PM,Lim B,Robson P,Lipovich L.Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells.RNA 2010;16:324-337[PMID:20026622 DOI:10.1261/rna.1441510]
454 Chakraborty D,Kappei D,Theis M,Nitzsche A,Ding L,Paszkowski-Rogacz M,Surendranath V,Berger N,Schulz H,Saar K,Hubner N,Buchholz F.Combined RNAi and localization for functionally dissecting long noncoding RNAs.Nat Methods 2012;9:360 -362[PMID:22327834 DOI:10.1038/nmeth.1894]
455 Ng SY,Johnson R,Stanton LW.Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors.EMBO J 2012;31 :522-533[PMID:22193719 DOI:10.1038/emboj.2011.459]
456 Gutschner T,H?mmerle M,Eissmann M,Hsu J,Kim Y,Hung G,Revenko A,Arun G,Stentrup M,Gross M,Z?rnig M,Mac Leod AR,Spector DL,Diederichs S.The noncoding RNA MALAT1is a critical regulator of the metastasis phenotype of lung cancer cells.Cancer Res 2013;73:1180-1189[PMID:23243023 DOI:10 .1158/0008-5472.CAN-12-2850]
457 Guo F,Li Y,Liu Y,Wang J,Li Y,Li G.Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaS ki human cervical cancer cells suppresses cell proliferation and invasion.Acta Biochim Biophys Sin(Shanghai)2010;42:224-229[PMID:20213048]
458 Jiang Y,Li Y,Fang S,Jiang B,Qin C,Xie P,Zhou G,Li G.The role of MALAT1 correlates with HPV in cervical cancer.Oncol Lett2014;7:2135-2141[PMID:24932303 DOI:10.3892/ol.2014.1996]
459 Gupta RA,Shah N,Wang KC,Kim J,Horlings HM,Wong DJ,Tsai MC,Hung T,Argani P,Rinn JL,Wang Y,Brzoska P,Kong B,Li R,West RB,van de Vijver MJ,Sukumar S,Chang HY.Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis.Nature 2010;464:1071-1076[PMID:20393566DOI:10.1038/nature08975]
460 Geng YJ,Xie SL,Li Q,Ma J,Wang GY.Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression.J Int Med Res 2011;39:2119-2128[PMID:22289527]
461 Zhang Y,Xia J,Li Q,Yao Y,Eades G,Gernapudi R,Duru N,Kensler TW,Zhou Q.NRF2/long noncoding RNA ROR signaling regulates mammary stem cell expansion and protects against estrogen genotoxicity.J Biol Chem 2014;289:31310-31318[PMID:25231996 DOI:10.1074/jbc.M114.604868]
462 Marcato P,Dean CA,Giacomantonio CA,Lee PW.Aldehyde dehydrogenase:its role as a cancer stem cell marker comes down to the specific isoform.Cell Cycle 2011;10:1378-1384[PMID:21552008]
463 Miranda-Lorenzo I,Dorado J,Lonardo E,Alcala S,Serrano AG,Clausell-Tormos J,Cioffi M,Megias D,Zagorac S,Balic A,Hidalgo M,Erkan M,Kleeff J,Scarpa A,Sainz B,Heeschen C.Intracellular autofluorescence:a biomarker for epithelial cancer stem cells.Nat Methods 2014;11:1161-1169[PMID:25262208DOI:10.1038/nmeth.3112]
464 Takahashi-Yanaga F,Kahn M.Targeting Wnt signaling:can we safely eradicate cancer stem cells?Clin Cancer Res 2010;16 :3153-3162[PMID:20530697 DOI:10.1158/1078-0432.CCR-09-2943]
465 Justilien V,Fields AP.Molecular pathways:novel approaches for improved therapeutic targeting of Hedgehog signaling in cancer stem cells.Clin Cancer Res 2015;21:505-513[PMID:25646180DOI:10.1158/1078-0432.CCR-14-0507]
466 Kim J,Orkin SH.Embryonic stem cell-specific signatures in cancer:insights into genomic regulatory networks and implications for medicine.Genome Med 2011;3:75[PMID:22126538 DOI:10 .1186/gm291]
467 Rowland BD,Peeper DS.KLF4,p21 and context-dependent opposing forces in cancer.Nat Rev Cancer 2006;6:11-23[PMID:16372018 DOI:10.1038/nrc1780]
468 Yori JL,Seachrist DD,Johnson E,Lozada KL,Abdul-Karim FW,Chodosh LA,Schiemann WP,Keri RA.Krüppel-like factor 4inhibits tumorigenic progression and metastasis in a mouse model of breast cancer.Neoplasia 2011;13:601-610[PMID:21750654]
469 Iv Santaliz-Ruiz LE,Xie X,Old M,Teknos TN,Pan Q.Emerging role of nanog in tumorigenesis and cancer stem cells.Int J Cancer2014;135:2741-2748[PMID:24375318 DOI:10.1002/ijc.28690]
470 SuvàML,Riggi N,Bernstein BE.Epigenetic reprogramming in cancer.Science 2013;339:1567-1570[PMID:23539597 DOI:10 .1126/science.1230184]
471 Mu?oz P,Iliou MS,Esteller M.Epigenetic alterations involved in cancer stem cell reprogramming.Mol Oncol 2012;6:620-636[PMID:23141800 DOI:10.1016/j.molonc.2012.10.006]
472 Kim J,Zaret KS.Reprogramming of human cancer cells to pluripotency for models of cancer progression.EMBO J 2015;34:739 -747[PMID:25712212 DOI:10.15252/embj.201490736]
473 Knoepfler PS.Deconstructing stem cell tumorigenicity:a roadmap to safe regenerative medicine.Stem Cells 2009;27:1050-1056[PMID:19415771 DOI:10.1002/stem.37]
474 Bianco C,Rangel MC,Castro NP,Nagaoka T,Rollman K,Gonzales M,Salomon DS.Role of Cripto-1 in stem cell maintenance and malignant progression.Am J Pathol 2010;177:532-540[PMID:20616345 DOI:10.2353/ajpath.2010.100102]
475 Pacheco-Pinedo EC,Durham AC,Stewart KM,Goss AM,Lu MM,Demayo FJ,Morrisey EE.Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium.J Clin Invest 2011;121:1935-1945[PMID:21490395 DOI:10.1172/JCI44871]
476 Lukacs RU,Memarzadeh S,Wu H,Witte ON.Bmi-1 is a crucial regulator of prostate stem cell self-renewal and malignant transformation.Cell Stem Cell 2010;7:682-693[PMID:21112563DOI:10.1016/j.stem.2010.11.013]
477 di Martino E,Tomlinson DC,Knowles MA.A Decade of FGF Receptor Research in Bladder Cancer:Past,Present,and Future Challenges.Adv Urol 2012;2012:429213[PMID:22899908 DOI:10 .1155/2012/429213]
2 Thomson JA,Itskovitz-Eldor J,Shapiro SS,Waknitz MA,Swiergiel JJ,Marshall VS,Jones JM.Embryonic stem cell lines derived from human blastocysts.Science 1998;282:1145-1147[PMID:9804556]
3 Tesar PJ,Chenoweth JG,Brook FA,Davies TJ,Evans EP,Mack DL,Gardner RL,McK ay RD.New cell lines from mouse epiblast share defining features with human embryonic stem cells.Nature2007;448:196-199[PMID:17597760]
4 Boyer LA,Lee TI,Cole MF,Johnstone SE,Levine SS,Zucker JP,Guenther MG,Kumar RM,Murray HL,Jenner RG,Gifford DK,Melton DA,Jaenisch R,Young RA.Core transcriptional regulatory circuitry in human embryonic stem cells.Cell 2005;122:947-956[PMID:16153702 DOI:10.1016/j.cell.2005.08.020]
5 Theunissen TW,Jaenisch R.Molecular control of induced pluripotency.Cell Stem Cell 2014;14:720-734[PMID:24905163DOI:10.1016/j.stem.2014.05.002]
6 Cherry AB,Daley GQ.Reprogrammed cells for disease modeling and regenerative medicine.Annu Rev Med 2013;64:277-290[PMID:23327523 DOI:10.1146/annurev-med-050311-163324]
7 Solter D.From teratocarcinomas to embryonic stem cells and beyond:a history of embryonic stem cell research.Nat Rev Genet2006;7:319-327[PMID:16534514 DOI:10.1038/nrg1827]
8 Friedmann-Morvinski D,Verma IM.Dedifferentiation and reprogramming:origins of cancer stem cells.EMBO Rep 2014;15:244 -253[PMID:24531722 DOI:10.1002/embr.201338254]
9 Goding CR,Pei D,Lu X.Cancer:pathological nuclear reprog-ramming?Nat Rev Cancer 2014;14:568-573[PMID:25030952 DOI:10 .1038/nrc3781]
10 Kreso A,Dick JE.Evolution of the cancer stem cell model.Cell Stem Cell 2014;14:275-291[PMID:24607403 DOI:10.1016/j.stem.2014.02.006]
11 Lobo NA,Shimono Y,Qian D,Clarke MF.The biology of cancer stem cells.Annu Rev Cell Dev Biol 2007;23:675-699[PMID:17645413]
12 O’Connor ML,Xiang D,Shigdar S,Macdonald J,Li Y,Wang T,Pu C,Wang Z,Qiao L,Duan W.Cancer stem cells:A contentious hypothesis now moving forward.Cancer Lett 2014;344:180-187[PMID:24333726 DOI:10.1016/j.canlet.2013.11.012]
13 Pattabiraman DR,Weinberg RA.Tackling the cancer stem cells-what challenges do they pose?Nat Rev Drug Discov 2014;13:497 -512[PMID:24981363 DOI:10.1038/nrd4253]
14 Li R,Liang J,Ni S,Zhou T,Qing X,Li H,He W,Chen J,Li F,Zhuang Q,Qin B,Xu J,Li W,Yang J,Gan Y,Qin D,Feng S,Song H,Yang D,Zhang B,Zeng L,Lai L,Esteban MA,Pei D.A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts.Cell Stem Cell 2010;7:51 -63[PMID:20621050 DOI:10.1016/j.stem.2010.04.014]
15 Ben-Porath I,Thomson MW,Carey VJ,Ge R,Bell GW,Regev A,Weinberg RA.An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors.Nat Genet 2008;40:499-507[PMID:18443585 DOI:10.1038/ng.127]
16 Wong DJ,Liu H,Ridky TW,Cassarino D,Segal E,Chang HY.Module map of stem cell genes guides creation of epithelial cancer stem cells.Cell Stem Cell 2008;2:333-344[PMID:18397753 DOI:10 .1016/j.stem.2008.02.009]
17 Zhao W,Ji X,Zhang F,Li L,Ma L.Embryonic stem cell markers.Molecules 2012;17:6196-6236[PMID:22634835 DOI:10.3390/molecules17066196]
18 Knowles BB,Aden DP,Solter D.Monoclonal antibody detecting a stage-specific embryonic antigen(SSEA-1)on preimplantation mouse embryos and teratocarcinoma cells.Curr Top Microbiol Immunol 1978;81:51-53[PMID:688761]
19 Solter D,Knowles BB.Monoclonal antibody defining a stage-specific mouse embryonic antigen(SSEA-1).Proc Natl Acad Sci USA 1978;75:5565-5569[PMID:281705]
20 Henderson JK,Draper JS,Baillie HS,Fishel S,Thomson JA,Moore H,Andrews PW.Preimplantation human embryos and embryonic stem cells show comparable expression of stage-specific embryonic antigens.Stem Cells 2002;20:329-337[PMID:12110702 DOI:10.1634/stemcells.20-4-329]
21 Kannagi R,Levery SB,Ishigami F,Hakomori S,Shevinsky LH,Knowles BB,Solter D.New globoseries glycosphingolipids in human teratocarcinoma reactive with the monoclonal antibody directed to a developmentally regulated antigen,stage-specific embryonic antigen 3.J Biol Chem 1983;258:8934-8942[PMID:6863318]
22 Shevinsky LH,Knowles BB,Damjanov I,Solter D.Monoclonal antibody to murine embryos defines a stage-specific embryonic antigen expressed on mouse embryos and human teratocarcinoma cells.Cell 1982;30:697-705[PMID:6183004]
23 Giwercman A,Andrews PW,J?rgensen N,Müller J,Graem N,Skakkebaek NE.Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis.Cancer 1993;72:1308-1314[PMID:8339218]
24 Schopperle WM,De Wolf WC.The TRA-1-60 and TRA-1-81human pluripotent stem cell markers are expressed on podocalyxin in embryonal carcinoma.Stem Cells 2007;25:723-730[PMID:17124010]
25 Tanabe K,Nakamura M,Narita M,Takahashi K,Yamanaka S.Maturation,not initiation,is the major roadblock during reprogramming toward pluripotency from human fibroblasts.Proc Natl Acad Sci USA 2013;110:12172-12179[PMID:23812749DOI:10.1073/pnas.1310291110]
26 Sundberg M,Jansson L,Ketolainen J,Pihlajam?ki H,Suuronen R,Skottman H,Inzunza J,Hovatta O,Narkilahti S.CD marker expression profiles of human embryonic stem cells and their neural derivatives,determined using flow-cytometric analysis,reveal a novel CD marker for exclusion of pluripotent stem cells.Stem Cell Res 2009;2:113-124[PMID:19383417 DOI:10.1016/j.scr.2008.08.001]
27 Evseenko D,Zhu Y,Schenke-Layland K,Kuo J,Latour B,Ge S,Scholes J,Dravid G,Li X,MacL ellan WR,Crooks GM.Mapping the first stages of mesoderm commitment during differentiation of human embryonic stem cells.Proc Natl Acad Sci USA 2010;107:13742-13747[PMID:20643952 DOI:10.1073/pnas.1002077107]
28 Klauzinska M,Castro NP,Rangel MC,Spike BT,Gray PC,Bertolette D,Cuttitta F,Salomon D.The multifaceted role of the embryonic gene Cripto-1 in cancer,stem cells and epithelial-mesenchymal transition.Semin Cancer Biol 2014;29:51-58[PMID:25153355 DOI:10.1016/j.semcancer.2014.08.003]
29 Parish CL,Parisi S,Persico MG,Arenas E,Minchiotti G.Cripto as a target for improving embryonic stem cell-based therapy in Parkinson’s disease.Stem Cells 2005;23:471-476[PMID:15790767]
30 Al-Hajj M,Wicha MS,Benito-Hernandez A,Morrison SJ,Clarke MF.Prospective identification of tumorigenic breast cancer cells.Proc Natl Acad Sci USA 2003;100:3983-3988[PMID:12629218DOI:10.1073/pnas.0530291100]
31 Kim MP,Fleming JB,Wang H,Abbruzzese JL,Choi W,Kopetz S,McC onkey DJ,Evans DB,Gallick GE.ALDH activity selectively defines an enhanced tumor-initiating cell population relative to CD133 expression in human pancreatic adenocarcinoma.PLo S One 2011;6:e20636[PMID:21695188 DOI:10.1371/journal.pone.0020636]
32 Afify A,Purnell P,Nguyen L.Role of CD44s and CD44v6 on human breast cancer cell adhesion,migration,and invasion.Exp Mol Pathol 2009;86:95-100[PMID:19167378 DOI:10.1016/j.yexmp.2008.12.003]
33 Bourguignon LY,Spevak CC,Wong G,Xia W,Gilad E.Hyaluro-nan-CD44 interaction with protein kinase C(epsilon)promotes oncogenic signaling by the stem cell marker Nanog and the Production of micro RNA-21,leading to down-regulation of the tumor suppressor protein PDCD4,anti-apoptosis,and chemotherapy resistance in breast tumor cells.J Biol Chem 2009;284:26533-26546[PMID:19633292 DOI:10.1074/jbc.M109.027466]
34 Schabath H,Runz S,Joumaa S,Altevogt P.CD24 affects CXCR4function in pre-B lymphocytes and breast carcinoma cells.J Cell Sci 2006;119:314-325[PMID:16390867]
35 Allan AL.Cancer stem cells in solid tumors.New York:Humana Press,2011
36 Huang EH,Hynes MJ,Zhang T,Ginestier C,Dontu G,Appelman H,Fields JZ,Wicha MS,Boman BM.Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells(SC)and tracks SC overpopulation during colon tumorigenesis.Cancer Res 2009;69:3382-3389[PMID:19336570 DOI:10 .1158/0008-5472.CAN-08-4418]
37 Moreb JS.Aldehyde dehydrogenase as a marker for stem cells.Curr Stem Cell Res Ther 2008;3:237-246[PMID:19075754]
38 Singh SK,Clarke ID,Terasaki M,Bonn VE,Hawkins C,Squire J,Dirks PB.Identification of a cancer stem cell in human brain tumors.Cancer Res 2003;63:5821-5828[PMID:14522905]
39 Irollo E,Pirozzi G.CD133:to be or not to be,is this the real question?Am J Transl Res 2013;5:563-581[PMID:24093054]
40 Salnikov AV,Gladkich J,Moldenhauer G,Volm M,Mattern J,Herr I.CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients.Int J Cancer 2010;126:950-958[PMID:19676044DOI:10.1002/ijc.24822]
41 Beier D,Hau P,Proescholdt M,Lohmeier A,Wischhusen J,Oefner PJ,Aigner L,Brawanski A,Bogdahn U,Beier CP.CD133(+)and CD133(-)glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles.Cancer Res 2007;67:4010-4015[PMID:17483311]
42 Hemmati HD,Nakano I,Lazareff JA,Masterman-Smith M,Geschwind DH,Bronner-Fraser M,Kornblum HI.Cancerous stem cells can arise from pediatric brain tumors.Proc Natl Acad Sci USA 2003;100:15178-15183[PMID:14645703 DOI:10.1073/pnas.2036535100]
43 Zinzi L,Capparelli E,Cantore M,Contino M,Leopoldo M,Colabufo NA.Small and Innovative Molecules as New Strategy to Revert MDR.Front Oncol 2014;4:2[PMID:24478983 DOI:10 .3389/fonc.2014.00002]
44 Choi YH,Yu AM.ABC transporters in multidrug resistance and pharmacokinetics,and strategies for drug development.Curr Pharm Des 2014;20:793-807[PMID:23688078]
45 Read TA,Fogarty MP,Markant SL,McL endon RE,Wei Z,Ellison DW,Febbo PG,Wechsler-Reya RJ.Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma.Cancer Cell 2009;15:135-147[PMID:19185848 DOI:10.1016/j.ccr.2008.12.016]
46 Gao MQ,Choi YP,Kang S,Youn JH,Cho NH.CD24+cells from hierarchically organized ovarian cancer are enriched in cancer stem cells.Oncogene 2010;29:2672-2680[PMID:20190812 DOI:10 .1038/onc.2010.35]
47 Ishiwata T,Teduka K,Yamamoto T,Kawahara K,Matsuda Y,Naito Z.Neuroepithelial stem cell marker nestin regulates the migration,invasion and growth of human gliomas.Oncol Rep 2011;26 :91-99[PMID:21503585 DOI:10.3892/or.2011.1267]
48 Nakai E,Park K,Yawata T,Chihara T,Kumazawa A,Nakabayashi H,Shimizu K.Enhanced MDR1 expression and chemoresistance of cancer stem cells derived from glioblastoma.Cancer Invest 2009;27:901 -908[PMID:19832037 DOI:10.3109/07357900801946679]
49 Ricci-Vitiani L,Lombardi DG,Pilozzi E,Biffoni M,Todaro M,Peschle C,De Maria R.Identification and expansion of human colon-cancer-initiating cells.Nature 2007;445:111-115[PMID:17122771]
50 Trzpis M,McL aughlin PM,de Leij LM,Harmsen MC.Epithelial cell adhesion molecule:more than a carcinoma marker and adhesion molecule.Am J Pathol 2007;171:386-395[PMID:17600130 DOI:10 .2353/ajpath.2007.070152]
51 Dalerba P,Dylla SJ,Park IK,Liu R,Wang X,Cho RW,Hoey T,Gurney A,Huang EH,Simeone DM,Shelton AA,Parmiani G,Castelli C,Clarke MF.Phenotypic characterization of human colorectal cancer stem cells.Proc Natl Acad Sci USA 2007;104:10158-10163[PMID:17548814 DOI:10.1073/pnas.0703478104]
52 Weidle UH,Eggle D,Klostermann S,Swart GW.ALCAM/CD166:cancer-related issues.Cancer Genomics Proteomics 2010;7:231 -243[PMID:20952758]
53 Brizzi MF,Tarone G,Defilippi P.Extracellular matrix,integrins,and growth factors as tailors of the stem cell niche.Curr Opin Cell Biol 2012;24:645-651[PMID:22898530 DOI:10.1016/j.ceb.2012.07.001]
54 Wu XS,Xi HQ,Chen L.Lgr5 is a potential marker of colorectal carcinoma stem cells that correlates with patient survival.World J Surg Oncol 2012;10:244[PMID:23153436 DOI:10.1186/1477-7819 -10-244]
55 de Lau WB,Snel B,Clevers HC.The R-spondin protein family.Genome Biol 2012;13:242[PMID:22439850 DOI:10.1186/gb-2012-13-3-242]
56 Takahashi H,Ishii H,Nishida N,Takemasa I,Mizushima T,Ikeda M,Yokobori T,Mimori K,Yamamoto H,Sekimoto M,Doki Y,Mori M.Significance of Lgr5(+ve)cancer stem cells in the colon and rectum.Ann Surg Oncol 2011;18:1166-1174[PMID:21125339 DOI:10.1245/s10434-010-1373-9]
57 Li C,Heidt DG,Dalerba P,Burant CF,Zhang L,Adsay V,Wicha M,Clarke MF,Simeone DM.Identification of pancreatic cancer stem cells.Cancer Res 2007;67:1030-1037[PMID:17283135]
58 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]
59 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]
60 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]
61 Sharpe B,Beresford M,Bowen R,Mitchard J,Chalmers AD.Searching for prostate cancer stem cells:markers and methods.Stem Cell Rev 2013;9:721-730[PMID:23775699 DOI:10.1007/s12015-013-9453-4]
62 Tomao F,Papa A,Strudel M,Rossi L,Lo Russo G,Benedetti Panici P,Ciabatta FR,Tomao S.Investigating molecular profiles of ovarian cancer:an update on cancer stem cells.J Cancer 2014;5:301 -310[PMID:24723972 DOI:10.7150/jca.8610]
63 Luo L,Zeng J,Liang B,Zhao Z,Sun L,Cao D,Yang J,Shen K.Ovarian cancer cells with the CD117 phenotype are highly tumorigenic and are related to chemotherapy outcome.Exp Mol Pathol 2011;91:596 -602[PMID:21787767 DOI:10.1016/j.yexmp.2011.06.005]
64 La Porta CA,Zapperi S.Human breast and melanoma cancer stem cells biomarkers.Cancer Lett 2013;338:69-73[PMID:22445909DOI:10.1016/j.canlet.2012.03.017]
65 Monzani E,Facchetti F,Galmozzi E,Corsini E,Benetti A,Cavazzin C,Gritti A,Piccinini A,Porro D,Santinami M,Invernici G,Parati E,Alessandri G,La Porta CA.Melanoma contains CD133and ABCG2 positive cells with enhanced tumourigenic potential.Eur J Cancer 2007;43:935-946[PMID:17320377]
66 Redmer T,Welte Y,Behrens D,Fichtner I,Przybilla D,Wruck W,Yaspo ML,Lehrach H,Sch?fer R,Regenbrecht CR.The nerve growth factor receptor CD271 is crucial to maintain tumorigenicity and stem-like properties of melanoma cells.PLo S One 2014;9:e92596[PMID:24799129 DOI:10.1371/journal.pone.0092596]
67 Taghizadeh R,Noh M,Huh YH,Ciusani E,Sigalotti L,Maio M,Arosio B,Nicotra MR,Natali P,Sherley JL,La Porta CA.CXCR6,a newly defined biomarker of tissue-specific stem cell asymmetric self-renewal,identifies more aggressive human melanoma cancer stem cells.PLo S One 2010;5:e15183[PMID:21203549 DOI:10 .1371/journal.pone.0015183]
68 Kumar SM,Liu S,Lu H,Zhang H,Zhang PJ,Gimotty PA,Guerra M,Guo W,Xu X.Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation.Oncogene 2012;31:4898-4911[PMID:22286766 DOI:10.1038/onc.2011.656]
69 Eramo A,Lotti F,Sette G,Pilozzi E,Biffoni M,Di Virgilio A,Conticello C,Ruco L,Peschle C,De Maria R.Identification and expansion of the tumorigenic lung cancer stem cell population.Cell Death Differ 2008;15:504-514[PMID:18049477]
70 Chen YC,Hsu HS,Chen YW,Tsai TH,How CK,Wang CY,Hung SC,Chang YL,Tsai ML,Lee YY,Ku HH,Chiou SH.Oct4expression maintained cancer stem-like properties in lung cancer-derived CD133-positive cells.PLo S One 2008;3:e2637[PMID:18612434 DOI:10.1371/journal.pone.0002637]
71 Kimura M,Takenobu H,Akita N,Nakazawa A,Ochiai H,Shimozato O,Fujimura Y,Koseki H,Yoshino I,Kimura H,Nakagawara A,Kamijo T.Bmi1 regulates cell fate via tumor suppressor WWOX repression in small-cell lung cancer cells.Cancer Sci 2011;102:983-990[PMID:21276135 DOI:10.1111/j.1349-7006.2011.01891.x]
72 Yin S,Li J,Hu C,Chen X,Yao M,Yan M,Jiang G,Ge C,Xie H,Wan D,Yang S,Zheng S,Gu J.CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity.Int J Cancer 2007;120:1444-1450[PMID:17205516]
73 Mishra L,Banker T,Murray J,Byers S,Thenappan A,He AR,Shetty K,Johnson L,Reddy EP.Liver stem cells and hepatocellular carcinoma.Hepatology 2009;49:318-329[PMID:19111019 DOI:10 .1002/hep.22704]
74 Ji J,Wang XW.Clinical implications of cancer stem cell biology in hepatocellular carcinoma.Semin Oncol 2012;39:461-472[PMID:22846863 DOI:10.1053/j.seminoncol.2012.05.011]
75 Prince ME,Sivanandan R,Kaczorowski A,Wolf GT,Kaplan MJ,Dalerba P,Weissman IL,Clarke MF,Ailles LE.Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma.Proc Natl Acad Sci USA 2007;104:973 -978[PMID:17210912]
76 Okamoto A,Chikamatsu K,Sakakura K,Hatsushika K,Takahashi G,Masuyama K.Expansion and characterization of cancer stem- like cells in squamous cell carcinoma of the head and neck.Oral Oncol 2009;45:633-639[PMID:19027347 DOI:10.1016/j.oralon cology.2008.10.003]
77 Major AG,Pitty LP,Farah CS.Cancer stem cell markers in head and neck squamous cell carcinoma.Stem Cells Int 2013;2013:319489[PMID:23533441 DOI:10.1155/2013/319489]
78 Dreesen O,Brivanlou AH.Signaling pathways in cancer and embryonic stem cells.Stem Cell Rev 2007;3:7-17[PMID:17873377]
79 Takebe N,Harris PJ,Warren RQ,Ivy SP.Targeting cancer stem cells by inhibiting Wnt,Notch,and Hedgehog pathways.Nat Rev Clin Oncol 2011;8:97-106[PMID:21151206 DOI:10.1038/nrclinonc.2010.196]
80 Karamboulas C,Ailles L.Developmental signaling pathways in cancer stem cells of solid tumors.Biochim Biophys Acta 2013;1830:2481-2495[PMID:23196196 DOI:10.1016/j.bbagen.2012.11.008]
81 Niwa H,Burdon T,Chambers I,Smith A.Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3.Genes Dev 1998;12:2048-2060[PMID:9649508]
82 Frank DA.STAT3 as a central mediator of neoplastic cellular transformation.Cancer Lett 2007;251:199-210[PMID:17129668DOI:10.1016/j.canlet.2006.10.017]
83 Lin L,Liu A,Peng Z,Lin HJ,Li PK,Li C,Lin J.STAT3 is necessary for proliferation and survival in colon cancer-initiating cells.Cancer Res 2011;71:7226-7237[PMID:21900397 DOI:10 .1158/0008-5472.CAN-10-4660]
84 Kroon P,Berry PA,Stower MJ,Rodrigues G,Mann VM,Simms M,Bhasin D,Chettiar S,Li C,Li PK,Maitland NJ,Collins AT.JAK-STAT blockade inhibits tumor initiation and clonogenic recovery of prostate cancer stem-like cells.Cancer Res 2013;73:5288-5298[PMID:23824741 DOI:10.1158/0008-5472.CAN-13-0874]
85 Marotta LL,Almendro V,Marusyk A,Shipitsin M,Schemme J,Walker SR,Bloushtain-Qimron N,Kim JJ,Choudhury SA,Maruyama R,Wu Z,G?nen M,Mulvey LA,Bessarabova MO,Huh SJ,Silver SJ,Kim SY,Park SY,Lee HE,Anderson KS,Richardson AL,Nikolskaya T,Nikolsky Y,Liu XS,Root DE,Hahn WC,Frank DA,Polyak K.The JAK2/STAT3 signaling pathway is required for growth of CD44?CD24?stem cell-like breast cancer cells in human tumors.J Clin Invest 2011;121:2723-2735[PMID:21633165 DOI:10 .1172/JCI44745]
86 Logan CY,Nusse R.The Wnt signaling pathway in development and disease.Annu Rev Cell Dev Biol 2004;20:781-810[PMID:15473860 DOI:10.1146/annurev.cellbio.20.010403.113126]
87 Li VS,Ng SS,Boersema PJ,Low TY,Karthaus WR,Gerlach JP,Mohammed S,Heck AJ,Maurice MM,Mahmoudi T,Clevers H.Wnt signaling through inhibition ofβ-catenin degradation in an intact Axin1 complex.Cell 2012;149:1245-1256[PMID:22682247 DOI:10.1016/j.cell.2012.05.002]
88 He TC,Sparks AB,Rago C,Hermeking H,Zawel L,da Costa LT,Morin PJ,Vogelstein B,Kinzler KW.Identification of c-MYC as a target of the APC pathway.Science 1998;281:1509-1512[PMID:9727977]
89 Tetsu O,McC ormick F.Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.Nature 1999;398:422-426[PMID:10201372 DOI:10.1038/18884]
90 ten Berge D,Kurek D,Blauwkamp T,Koole W,Maas A,Eroglu E,Siu RK,Nusse R.Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells.Nat Cell Biol 2011;13:1070-1075[PMID:21841791 DOI:10.1038/ncb2314]
91 Sato N,Meijer L,Skaltsounis L,Greengard P,Brivanlou AH.Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor.Nat Med 2004;10:55-63[PMID:14702635 DOI:10.1038/nm979]
92 Wray J,Kalkan T,Gomez-Lopez S,Eckardt D,Cook A,Kemler R,Smith A.Inhibition of glycogen synthase kinase-3 alleviates Tcf3repression of the pluripotency network and increases embryonic stem cell resistance to differentiation.Nat Cell Biol 2011;13:838 -845[PMID:21685889 DOI:10.1038/ncb2267]
93 Valenta T,Gay M,Steiner S,Draganova K,Zemke M,Hoffmans R,Cinelli P,Aguet M,Sommer L,Basler K.Probing transcription-specific outputs ofβ-catenin in vivo.Genes Dev 2011;25:2631-2643[PMID:22190459 DOI:10.1101/gad.181289.111]
94 Holland JD,Klaus A,Garratt AN,Birchmeier W.Wnt signaling in stem and cancer stem cells.Curr Opin Cell Biol 2013;25:254-264[PMID:23347562 DOI:10.1016/j.ceb.2013.01.004]
95 Niwa H.Wnt:what’s needed to maintain pluripotency?Nat Cell Biol 2011;13:1024-1026[PMID:21892143 DOI:10.1038/ncb2333]
96 Kelly KF,Ng DY,Jayakumaran G,Wood GA,Koide H,Doble BW.β-catenin enhances Oct4 activity and reinforces pluripotency through a TCF-independent mechanism.Cell Stem Cell 2011;8:214 -227[PMID:21295277 DOI:10.1016/j.stem.2010.12.010]
97 Davidson KC,Adams AM,Goodson JM,Mc Donald CE,Potter JC,Berndt JD,Biechele TL,Taylor RJ,Moon RT.Wnt/β-catenin signaling promotes differentiation,not self-renewal,of human embryonic stem cells and is repressed by Oct4.Proc Natl Acad Sci U S A 2012;109:4485-4490[PMID:22392999 DOI:10.1073/pnas.1118777109]
98 Blauwkamp TA,Nigam S,Ardehali R,Weissman IL,Nusse R.Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors.Nat Commun 2012;3:1070[PMID:22990866 DOI:10.1038/ncomms2064]
99 Barker N,Ridgway RA,van Es JH,van de Wetering M,Begthel H,van den Born M,Danenberg E,Clarke AR,Sansom OJ,Clevers H.Crypt stem cells as the cells-of-origin of intestinal cancer.Nature2009;457:608-611[PMID:19092804 DOI:10.1038/nature07602]
100 Schepers AG,Snippert HJ,Stange DE,van den Born M,van Es JH,van de Wetering M,Clevers H.Lineage tracing reveals Lgr5+stem cell activity in mouse intestinal adenomas.Science 2012;337:730 -735[PMID:22855427 DOI:10.1126/science.1224676]
101 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]
102 Shackleton M,Vaillant F,Simpson KJ,Stingl J,Smyth GK,Asselin-Labat ML,Wu L,Lindeman GJ,Visvader JE.Generation of a functional mammary gland from a single stem cell.Nature 2006;439 :84-88[PMID:16397499]
103 Malanchi I,Santamaria-Martínez A,Susanto E,Peng H,Lehr HA,Delaloye JF,Huelsken J.Interactions between cancer stem cells and their niche govern metastatic colonization.Nature 2012;481:85-89[PMID:22158103 DOI:10.1038/nature10694]
104 Qu Q,Sun G,Li W,Yang S,Ye P,Zhao C,Yu RT,Gage FH,Evans RM,Shi Y.Orphan nuclear receptor TLX activates Wnt/beta-catenin signalling to stimulate neural stem cell proliferation and self-renewal.Nat Cell Biol 2010;12:31-40;sup pp 1-9[PMID:20010817 DOI:10.1038/ncb2001]
105 Mazumdar J,O’Brien WT,Johnson RS,LaM anna JC,Chavez JC,Klein PS,Simon MC.O2 regulates stem cells through Wnt/β-catenin signalling.Nat Cell Biol 2010;12:1007-1013[PMID:20852629DOI:10.1038/ncb2102]
106 Santoyo-Ramos P,Likhatcheva M,García-Zepeda EA,Casta?eda-Patlán MC,Robles-Flores M.Hypoxia-inducible factors modulate the stemness and malignancy of colon cancer cells by playing opposite roles in canonical Wnt signaling.PLo S One 2014;9:e112580[PMID:25396735 DOI:10.1371/journal.pone.0112580]
107 Barakat MT,Humke EW,Scott MP.Learning from Jekyll to control Hyde:Hedgehog signaling in development and cancer.Trends Mol Med 2010;16:337-348[PMID:20696410 DOI:10 .1016/j.molmed.2010.05.003]
108 Wu SM,Choo AB,Yap MG,Chan KK.Role of Sonic hedgehog signaling and the expression of its components in human embryonic stem cells.Stem Cell Res 2010;4:38-49[PMID:19836325 DOI:10 .1016/j.scr.2009.09.002]
109 Heo JS,Lee MY,Han HJ.Sonic hedgehog stimulates mouse embryonic stem cell proliferation by cooperation of Ca2+/protein kinase C and epidermal growth factor receptor as well as Gli1activation.Stem Cells 2007;25:3069-3080[PMID:17901397 DOI:10 .1634/stemcells.2007-0550]
110 Scales SJ,de Sauvage FJ.Mechanisms of Hedgehog pathway activation in cancer and implications for therapy.Trends Pharmacol Sci 2009;30:303-312[PMID:19443052 DOI:10.1016/j.tips.2009.03.007]
111 Liu S,Dontu G,Mantle ID,Patel S,Ahn NS,Jackson KW,Suri P,Wicha MS.Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells.Cancer Res2006;66:6063-6071[PMID:16778178 DOI:10.1158/0008-5472.CAN-06-0054]
112 Clement V,Sanchez P,de Tribolet N,Radovanovic I,Ruiz i Altaba A.HEDGEHOG-GLI1 signaling regulates human glioma growth,cancer stem cell self-renewal,and tumorigenicity.Curr Biol 2007;17 :165-172[PMID:17196391 DOI:10.1016/j.cub.2006.11.033]
113 Bar EE,Chaudhry A,Lin A,Fan X,Schreck K,Matsui W,Piccirillo S,Vescovi AL,DiM eco F,Olivi A,Eberhart CG.Cyclopa-mine-mediated hedgehog pathway inhibition depletes stem-like cancer cells in glioblastoma.Stem Cells 2007;25:2524-2533[PMID:17628016 DOI:10.1634/stemcells.2007-0166]
114 Merchant AA,Matsui W.Targeting Hedgehog--a cancer stem cell pathway.Clin Cancer Res 2010;16:3130-3140[PMID:20530699DOI:10.1158/1078-0432.CCR-09-2846]
115 Feldmann G,Dhara S,Fendrich V,Bedja D,Beaty R,Mullendore M,Karikari C,Alvarez H,Iacobuzio-Donahue C,Jimeno A,Gabrielson KL,Matsui W,Maitra A.Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases:a new paradigm for combination therapy in solid cancers.Cancer Res2007;67:2187-2196[PMID:17332349 DOI:10.1158/0008-5472.CAN-06-3281]
116 Chiba S.Notch signaling in stem cell systems.Stem Cells 2006;24:2437-2447[PMID:16888285 DOI:10.1634/stemcells.2005-0661]
117 Lowell S,Benchoua A,Heavey B,Smith AG.Notch promotes neural lineage entry by pluripotent embryonic stem cells.PLoS Biol2006;4:e121[PMID:16594731]
118 Noggle SA,Weiler D,Condie BG.Notch signaling is inactive but inducible in human embryonic stem cells.Stem Cells 2006;24:1646-1653[PMID:16614005 DOI:10.1634/stemcells.2005-0314]
119 Fox V,Gokhale PJ,Walsh JR,Matin M,Jones M,Andrews PW.Cell-cell signaling through NOTCH regulates human embryonic stem cell proliferation.Stem Cells 2008;26:715-723[PMID:18055449 DOI:10.1634/stemcells.2007-0368]
120 Yu X,Zou J,Ye Z,Hammond H,Chen G,Tokunaga A,Mali P,Li YM,Civin C,Gaiano N,Cheng L.Notch signaling activation in human embryonic stem cells is required for embryonic,but not trophoblastic,lineage commitment.Cell Stem Cell 2008;2:461-471[PMID:18462696 DOI:10.1016/j.stem.2008.03.001]
121 Liu J,Sato C,Cerletti M,Wagers A.Notch signaling in the regulation of stem cell self-renewal and differentiation.Curr Top Dev Biol 2010;92:367-409[PMID:20816402 DOI:10.1016/S0070-2153(10)92012-7]
122 Koch U,Lehal R,Radtke F.Stem cells living with a Notch.Development 2013;140:689-704[PMID:23362343 DOI:10.1242/dev.080614]
123 Abel EV,Kim EJ,Wu J,Hynes M,Bednar F,Proctor E,Wang L,Dziubinski ML,Simeone DM.The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer.PLo S One 2014;9:e91983[PMID:24647545 DOI:10.1371/journal.pone.0091983]
124 Hoey T,Yen WC,Axelrod F,Basi J,Donigian L,Dylla S,Fitch-Bruhns M,Lazetic S,Park IK,Sato A,Satyal S,Wang X,Clarke MF,Lewicki J,Gurney A.DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency.Cell Stem Cell 2009;5:168 -177[PMID:19664991 DOI:10.1016/j.stem.2009.05.019]
125 Sikandar SS,Pate KT,Anderson S,Dizon D,Edwards RA,Waterman ML,Lipkin SM.NOTCH signaling is required for formation and self-renewal of tumor-initiating cells and for repression of secretory cell differentiation in colon cancer.Cancer Res 2010;70:1469-1478[PMID:20145124 DOI:10.1158/0008-5472.CAN-09-2557]
126 Fan X,Matsui W,Khaki L,Stearns D,Chun J,Li YM,Eberhart CG.Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors.Cancer Res 2006;66:7445-7452[PMID:16885340]
127 Hallahan AR,Pritchard JI,Hansen S,Benson M,Stoeck J,Hatton BA,Russell TL,Ellenbogen RG,Bernstein ID,Beachy PA,Olson JM.The Smo A1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas.Cancer Res 2004;64:7794-7800[PMID:15520185]
128 Ayyanan A,Civenni G,Ciarloni L,Morel C,Mueller N,Lefort K,Mandinova A,Raffoul W,Fiche M,Dotto GP,Brisken C.Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism.Proc Natl Acad Sci USA 2006;103:3799-3804[PMID:16501043 DOI:10.1073/pnas.0600065103]
129 Farnie G,Clarke RB,Spence K,Pinnock N,Brennan K,Anderson NG,Bundred NJ.Novel cell culture technique for primary ductal carcinoma in situ:role of Notch and epidermal growth factor receptor signaling pathways.J Natl Cancer Inst 2007;99:616-627[PMID:17440163]
130 Harrison H,Farnie G,Howell SJ,Rock RE,Stylianou S,Brennan KR,Bundred NJ,Clarke RB.Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor.Cancer Res2010;70:709-718[PMID:20068161 DOI:10.1158/0008-5472.CAN-09-1681]
131 Gallahan D,Callahan R.Mammary tumorigenesis in feral mice:identification of a new int locus in mouse mammary tumor virus(Czech II)-induced mammary tumors.J Virol 1987;61:66-74[PMID:3023708]
132 Derynck R.TGF-beta-receptor-mediated signaling.Trends Biochem Sci 1994;19:548-553[PMID:7846768]
133 Oshimori N,Fuchs E.The harmonies played by TGF-βin stem cell biology.Cell Stem Cell 2012;11:751-764[PMID:23217421 DOI:10 .1016/j.stem.2012.11.001]
134 James D,Levine AJ,Besser D,Hemmati-Brivanlou A.TGFbeta/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells.Development 2005;132 :1273-1282[PMID:15703277]
135 Ogawa K,Saito A,Matsui H,Suzuki H,Ohtsuka S,Shimosato D,Morishita Y,Watabe T,Niwa H,Miyazono K.Activin-Nodal signaling is involved in propagation of mouse embryonic stem cells.J Cell Sci 2007;120:55-65[PMID:17182901]
136 Vallier L,Alexander M,Pedersen RA.Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells.J Cell Sci 2005;118:4495-4509[PMID:16179608]
137 Qi X,Li TG,Hao J,Hu J,Wang J,Simmons H,Miura S,Mishina Y,Zhao GQ.BMP4 supports self-renewal of embryonic stem cells by inhibiting mitogen-activated protein kinase pathways.Proc Natl Acad Sci USA 2004;101:6027-6032[PMID:15075392 DOI:10 .1073/pnas.0401367101]
138 Ying QL,Nichols J,Chambers I,Smith A.BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3.Cell 2003;115:281-292[PMID:14636556]
139 Xu RH,Chen X,Li DS,Li R,Addicks GC,Glennon C,Zwaka TP,Thomson JA.BMP4 initiates human embryonic stem cell differentiation to trophoblast.Nat Biotechnol 2002;20:1261-1264[PMID:12426580 DOI:10.1038/nbt761]
140 Xu RH,Peck RM,Li DS,Feng X,Ludwig T,Thomson JA.Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells.Nat Methods 2005;2:185-190[PMID:15782187]
141 Zhang P,Li J,Tan Z,Wang C,Liu T,Chen L,Yong J,Jiang W,Sun X,Du L,Ding M,Deng H.Short-term BMP-4 treatment initiates mesoderm induction in human embryonic stem cells.Blood 2008;111:1933-1941[PMID:18042803 DOI:10.1182/blood-2007-02-074120]
142 Brons IG,Smithers LE,Trotter MW,Rugg-Gunn P,Sun B,Chuva de Sousa Lopes SM,Howlett SK,Clarkson A,Ahrlund-Richter L,Pedersen RA,Vallier L.Derivation of pluripotent epiblast stem cells from mammalian embryos.Nature 2007;448:191-195[PMID:17597762 DOI:10.1038/nature05950]
143 Smith AG.Embryo-derived stem cells:of mice and men.Annu Rev Cell Dev Biol 2001;17:435-462[PMID:11687496 DOI:10.1146/annurev.cellbio.17.1.435]
144 Beattie GM,Lopez AD,Bucay N,Hinton A,Firpo MT,King CC,Hayek A.Activin A maintains pluripotency of human embryonic stem cells in the absence of feeder layers.Stem Cells 2005;23:489 -495[PMID:15790770]
145 Xiao L,Yuan X,Sharkis SJ.Activin A maintains self-renewal and regulates fibroblast growth factor,Wnt,and bone morphogenic protein pathways in human embryonic stem cells.Stem Cells 2006;24 :1476-1486[PMID:16456129 DOI:10.1634/stemcells.2005-0299]
146 Vallier L,Reynolds D,Pedersen RA.Nodal inhibits differentiation of human embryonic stem cells along the neuroectodermal default pathway.Dev Biol 2004;275:403-421[PMID:15501227 DOI:10 .1016/j.ydbio.2004.08.031]
147 Vallier L,Mendjan S,Brown S,Chng Z,Teo A,Smithers LE,Trotter MW,Cho CH,Martinez A,Rugg-Gunn P,Brons G,Pedersen RA.Activin/Nodal signalling maintains pluripotency by controlling Nanog expression.Development 2009;136:1339-1349[PMID:19279133 DOI:10.1242/dev.033951]
148 Xu RH,Sampsell-Barron TL,Gu F,Root S,Peck RM,Pan G,Yu J,Antosiewicz-Bourget J,Tian S,Stewart R,Thomson JA.NANOG is a direct target of TGFbeta/activin-mediated SMAD signaling in human ESCs.Cell Stem Cell 2008;3:196-206[PMID:18682241DOI:10.1016/j.stem.2008.07.001]
149 Mullen AC,Orlando DA,Newman JJ,Lovén J,Kumar RM,Bilodeau S,Reddy J,Guenther MG,De Koter RP,Young RA.Master transcription factors determine cell-type-specific responses to TGF-βsignaling.Cell 2011;147:565-576[PMID:22036565DOI:10.1016/j.cell.2011.08.050]
150 Besser D.Expression of nodal,lefty-a,and lefty-B in undifferentiated human embryonic stem cells requires activation of Smad2/3.J Biol Chem 2004;279:45076-45084[PMID:15308665 DOI:10.1074/jbc.M404979200]
151 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 epithelial-mesenchymal transition generates cells with properties of stem cells.Cell 2008;133:704-715[PMID:18485877 DOI:10.1016/j.cell.2008.03.027]
152 Yang J,Weinberg RA.Epithelial-mesenchymal transition:at the crossroads of development and tumor metastasis.Dev Cell 2008;14 :818-829[PMID:18539112 DOI:10.1016/j.devcel.2008.05.009]
153 MassaguéJ.TGFbeta in Cancer.Cell 2008;134:215-230[PMID:18662538 DOI:10.1016/j.cell.2008.07.001]
154 Guasch G,Schober M,Pasolli HA,Conn EB,Polak L,Fuchs E.Loss of TGFbeta signaling destabilizes homeostasis and promotes squamous cell carcinomas in stratified epithelia.Cancer Cell 2007;12 :313-327[PMID:17936557 DOI:10.1016/j.ccr.2007.08.020]
155 Mc Lean GW,Komiyama NH,Serrels B,Asano H,Reynolds L,Conti F,Hodivala-Dilke K,Metzger D,Chambon P,Grant SG,Frame MC.Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression.Genes Dev2004;18:2998-3003[PMID:15601818]
156 Schober M,Fuchs E.Tumor-initiating stem cells of squamous cell carcinomas and their control by TGF-βand integrin/focal adhesion kinase(FAK)signaling.Proc Natl Acad Sci USA 2011;108:10544-10549[PMID:21670270 DOI:10.1073/pnas.1107807108]
157 Bhola NE,Balko JM,Dugger TC,Kuba MG,Sánchez V,Sanders M,Stanford J,Cook RS,Arteaga CL.TGF-βinhibition enhances chemotherapy action against triple-negative breast cancer.J Clin Invest 2013;123:1348-1358[PMID:23391723 DOI:10.1172/JCI65416]
158 Pe?uelas S,Anido J,Prieto-Sánchez RM,Folch G,Barba I,Cuartas I,García-Dorado D,Poca MA,Sahuquillo J,Baselga J,Seoane J.TGF-beta increases glioma-initiating cell self-renewal through the induction of LIF in human glioblastoma.Cancer Cell 2009;15:315 -327[PMID:19345330 DOI:10.1016/j.ccr.2009.02.011]
159 Ikushima H,Todo T,Ino Y,Takahashi M,Miyazawa K,Miyazono K.Autocrine TGF-beta signaling maintains tumorigenicity of glioma-initiating cells through Sry-related HMG-box factors.Cell Stem Cell 2009;5:504-514[PMID:19896441 DOI:10.1016/j.stem.2009.08.018]
160 Piccirillo SG,Reynolds BA,Zanetti N,Lamorte G,Binda E,Broggi G,Brem H,Olivi A,Dimeco F,Vescovi AL.Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells.Nature 2006;444:761-765[PMID:17151667]
161 Lee J,Son MJ,Woolard K,Donin NM,Li A,Cheng CH,Kotliarova S,Kotliarov Y,Walling J,Ahn S,Kim M,Totonchy M,Cusack T,Ene C,Ma H,Su Q,Zenklusen JC,Zhang W,Maric D,Fine HA.Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells.Cancer Cell 2008;13:69-80[PMID:18167341 DOI:10.1016/j.ccr.2007.12.005]
162 Lanner F,Rossant J.The role of FGF/Erk signaling in pluripotent cells.Development 2010;137:3351-3360[PMID:20876656 DOI:10 .1242/dev.050146]
163 Turner N,Grose R.Fibroblast growth factor signalling:from development to cancer.Nat Rev Cancer 2010;10:116-129[PMID:20094046 DOI:10.1038/nrc2780]
164 Kunath T,Saba-El-Leil MK,Almousailleakh M,Wray J,Meloche S,Smith A.FGF stimulation of the Erk1/2 signalling cascade triggers transition of pluripotent embryonic stem cells from self-renewal to lineage commitment.Development 2007;134:2895-2902[PMID:17660198]
165 Stavridis MP,Lunn JS,Collins BJ,Storey KG.A discrete period of FGF-induced Erk1/2 signalling is required for vertebrate neural specification.Development 2007;134:2889-2894[PMID:17660197]
166 Ying QL,Wray J,Nichols J,Batlle-Morera L,Doble B,Woodgett J,Cohen P,Smith A.The ground state of embryonic stem cell self-renewal.Nature 2008;453:519-523[PMID:18497825 DOI:10 .1038/nature06968]
167 Toyooka Y,Shimosato D,Murakami K,Takahashi K,Niwa H.Identification and characterization of subpopulations in undifferentiated ES cell culture.Development 2008;135:909-918[PMID:18263842 DOI:10.1242/dev.017400]
168 Amit M,Carpenter MK,Inokuma MS,Chiu CP,Harris CP,Waknitz MA,Itskovitz-Eldor J,Thomson JA.Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of culture.Dev Biol 2000;227:271 -278[PMID:11071754 DOI:10.1006/dbio.2000.9912]
169 Xu C,Inokuma MS,Denham J,Golds K,Kundu P,Gold JD,Carpenter MK.Feeder-free growth of undifferentiated human embryonic stem cells.Nat Biotechnol 2001;19:971-974[PMID:11581665 DOI:10.1038/nbt1001-971]
170 Wang G,Zhang H,Zhao Y,Li J,Cai J,Wang P,Meng S,Feng J,Miao C,Ding M,Li D,Deng H.Noggin and b FGF cooperate to maintain the pluripotency of human embryonic stem cells in the absence of feeder layers.Biochem Biophys Res Commun 2005;330:934 -942[PMID:15809086 DOI:10.1016/j.bbrc.2005.03.058]
171 Armstrong L,Hughes O,Yung S,Hyslop L,Stewart R,Wappler I,Peters H,Walter T,Stojkovic P,Evans J,Stojkovic M,Lako M.The role of PI3K/AKT,MAPK/ERK and NFkappabeta signalling in the maintenance of human embryonic stem cell pluripotency and viability highlighted by transcriptional profiling and functional analysis.Hum Mol Genet 2006;15:1894-1913[PMID:16644866]
172 Ding VM,Ling L,Natarajan S,Yap MG,Cool SM,Choo AB.FGF-2 modulates Wnt signaling in undifferentiated hE SC and iP S cells through activated PI3-K/GSK3beta signaling.J Cell Physiol2010;225:417-428[PMID:20506199 DOI:10.1002/jcp.22214]
173 Li J,Wang G,Wang C,Zhao Y,Zhang H,Tan Z,Song Z,Ding M,Deng H.MEK/ERK signaling contributes to the maintenance of human embryonic stem cell self-renewal.Differentiation 2007;75:299 -307[PMID:17286604 DOI:10.1111/j.1432-0436.2006.00143.x]
174 Li W,Wei W,Zhu S,Zhu J,Shi Y,Lin T,Hao E,Hayek A,Deng H,Ding S.Generation of rat and human induced pluripotent stem cells by combining genetic reprogramming and chemical inhibitors.Cell Stem Cell 2009;4:16-19[PMID:19097958 DOI:10.1016/j.stem.2008.11.014]
175 Xu Y,Zhu X,Hahm HS,Wei W,Hao E,Hayek A,Ding S.Revealing a core signaling regulatory mechanism for pluripotent stem cell survival and self-renewal by small molecules.Proc Natl Acad Sci USA 2010;107:8129-8134[PMID:20406903 DOI:10 .1073/pnas.1002024107]
176 Niwa H,Ogawa K,Shimosato D,Adachi K.A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells.Nature 2009;460:118-122[PMID:19571885 DOI:10.1038/nature08113]
177 Dirks PB.Brain tumor stem cells:bringing order to the chaos of brain cancer.J Clin Oncol 2008;26:2916-2924[PMID:18539973DOI:10.1200/JCO.2008.17.6792]
178 Ponti D,Costa A,Zaffaroni N,Pratesi G,Petrangolini G,Coradini D,Pilotti S,Pierotti MA,Daidone MG.Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties.Cancer Res 2005;65:5506-5511[PMID:15994920DOI:10.1158/0008-5472.CAN-05-0626]
179 Fillmore CM,Gupta PB,Rudnick JA,Caballero S,Keller PJ,Lander ES,Kuperwasser C.Estrogen expands breast cancer stem-like cells through paracrine FGF/Tbx3 signaling.Proc Natl Acad Sci USA 2010;107:21737-21742[PMID:21098263 DOI:10.1073/pnas.1007863107]
180 Guthridge MA,Seldin M,Basilico C.Induction of expression of growth-related genes by FGF-4 in mouse fibroblasts.Oncogene1996;12:1267-1278[PMID:8649829]
181 Fu M,Wang C,Li Z,Sakamaki T,Pestell RG.Minireview:Cyclin D1:normal and abnormal functions.Endocrinology 2004;145:5439-5447[PMID:15331580 DOI:10.1210/en.2004-0959]
182 McK eon F.p63 and the epithelial stem cell:more than status quo?Genes Dev 2004;18:465-469[PMID:15037544 DOI:10.1101/gad.1190504]
183 Kosaka N,Sakamoto H,Terada M,Ochiya T.Pleiotropic function of FGF-4:its role in development and stem cells.Dev Dyn 2009;238 :265-276[PMID:18792115 DOI:10.1002/dvdy.21699]
184 Loh YH,Wu Q,Chew JL,Vega VB,Zhang W,Chen X,Bourque G,George J,Leong B,Liu J,Wong KY,Sung KW,Lee CW,Zhao XD,Chiu KP,Lipovich L,Kuznetsov VA,Robson P,Stanton LW,Wei CL,Ruan Y,Lim B,Ng HH.The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.Nat Genet 2006;38:431-440[PMID:16518401 DOI:10.1038/ng1760]
185 Jaenisch R,Young R.Stem cells,the molecular circuitry of pluripotency and nuclear reprogramming.Cell 2008;132:567-582[PMID:18295576 DOI:10.1016/j.cell.2008.01.015]
186 Boyer LA,Plath K,Zeitlinger J,Brambrink T,Medeiros LA,Lee TI,Levine SS,Wernig M,Tajonar A,Ray MK,Bell GW,Otte AP,Vidal M,Gifford DK,Young RA,Jaenisch R.Polycomb complexes repress developmental regulators in murine embryonic stem cells.Nature 2006;441:349-353[PMID:16625203 DOI:10.1038/nature04733]
187 Orkin SH,Hochedlinger K.Chromatin connections to pluripotency and cellular reprogramming.Cell 2011;145:835-850[PMID:21663790 DOI:10.1016/j.cell.2011.05.019]
188 Young RA.Control of the embryonic stem cell state.Cell 2011;144 :940-954[PMID:21414485 DOI:10.1016/j.cell.2011.01.032]
189 Kim J,Woo AJ,Chu J,Snow JW,Fujiwara Y,Kim CG,Cantor AB,Orkin SH.A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs.Cell 2010;143 :313-324[PMID:20946988 DOI:10.1016/j.cell.2010.09.010]
190 Orkin SH,Wang J,Kim J,Chu J,Rao S,Theunissen TW,Shen X,Levasseur DN.The transcriptional network controlling pluripotency in ES cells.Cold Spring Harb Symp Quant Biol 2008;73:195-202[PMID:19478325 DOI:10.1101/sqb.2008.72.001]
191 Chen X,Xu H,Yuan P,Fang F,Huss M,Vega VB,Wong E,Orlov YL,Zhang W,Jiang J,Loh YH,Yeo HC,Yeo ZX,Narang V,Govindarajan KR,Leong B,Shahab A,Ruan Y,Bourque G,Sung WK,Clarke ND,Wei CL,Ng HH.Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.Cell 2008;133:1106-1117[PMID:18555785 DOI:10.1016/j.cell.2008.04.043]
192 Hnisz D,Abraham BJ,Lee TI,Lau A,Saint-AndréV,Sigova AA,Hoke HA,Young RA.Super-enhancers in the control of cell identity and disease.Cell 2013;155:934-947[PMID:24119843DOI:10.1016/j.cell.2013.09.053]
193 Whyte WA,Orlando DA,Hnisz D,Abraham BJ,Lin CY,Kagey MH,Rahl PB,Lee TI,Young RA.Master transcription factors and mediator establish super-enhancers at key cell identity genes.Cell 2013;153:307-319[PMID:23582322 DOI:10.1016/j.cell.2013.03.035]
194 Takahashi K,Yamanaka S.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.Cell 2006;126:663-676[PMID:16904174]
195 Rosner MH,Vigano MA,Ozato K,Timmons PM,Poirier F,Rigby PW,Staudt LM.A POU-domain transcription factor in early stem cells and germ cells of the mammalian embryo.Nature 1990;345:686 -692[PMID:1972777 DOI:10.1038/345686a0]
196 Sch?ler HR,Dressler GR,Balling R,Rohdewohld H,Gruss P.Oct4:a germline-specific transcription factor mapping to the mouse t-complex.EMBO J 1990;9:2185-2195[PMID:2357966]
197 Cauffman G,Van de Velde H,Liebaers I,Van Steirteghem A.Oct4 mR NA and protein expression during human preimplantation development.Mol Hum Reprod 2005;11:173-181[PMID:15695770]
198 Nichols J,Zevnik B,Anastassiadis K,Niwa H,Klewe-Nebenius D,Chambers I,Sch?ler H,Smith A.Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4.Cell 1998;95:379-391[PMID:9814708]
199 Nichols J,Evans EP,Smith AG.Establishment of germ-line-competent embryonic stem(ES)cells using differentiation inhibiting activity.Development 1990;110:1341-1348[PMID:2129226]
200 Niwa H,Miyazaki J,Smith AG.Quantitative expression of Oct-3/4 defines differentiation,dedifferentiation or self-renewal of ES cells.Nat Genet 2000;24:372-376[PMID:10742100 DOI:10 .1038/74199]
201 Shimozaki K,Nakashima K,Niwa H,Taga T.Involvement of Oct3/4 in the enhancement of neuronal differentiation of ES cells in neurogenesis-inducing cultures.Development 2003;130:2505-2512[PMID:12702663]
202 Aksoy I,Jauch R,Chen J,Dyla M,Divakar U,Bogu GK,Teo R,Leng Ng CK,Herath W,Lili S,Hutchins AP,Robson P,Kolatkar PR,Stanton LW.Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm.EMBO J 2013;32 :938-953[PMID:23474895 DOI:10.1038/emboj.2013.31]
203 Atlasi Y,Mowla SJ,Ziaee SA,Bahrami AR.Oct4,an embryonic stem cell marker,is highly expressed in bladder cancer.Int J Cancer2007;120:1598-1602[PMID:17205510 DOI:10.1002/ijc.22508]
204 Ezeh UI,Turek PJ,Reijo RA,Clark AT.Human embryonic stem cell genes OCT4,NANOG,STELLAR,and GDF3 are expressed in both seminoma and breast carcinoma.Cancer 2005;104:2255-2265[PMID:16228988 DOI:10.1002/cncr.21432]
205 Gu G,Yuan J,Wills M,Kasper S.Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo.Cancer Res 2007;67:4807-4815[PMID:17510410]
206 Liu CG,Lu Y,Wang BB,Zhang YJ,Zhang RS,Lu Y,Chen B,Xu H,Jin F,Lu P.Clinical implications of stem cell gene Oct4 expression in breast cancer.Ann Surg 2011;253:1165-1171[PMID:21394007DOI:10.1097/SLA.0b013e318214c54e]
207 Hu T,Liu S,Breiter DR,Wang F,Tang Y,Sun S.Octamer 4 small interfering RNA results in cancer stem cell-like cell apoptosis.Cancer Res 2008;68:6533-6540[PMID:18701476 DOI:10 .1158/0008-5472.CAN-07-6642]
208 Chiou SH,Yu CC,Huang CY,Lin SC,Liu CJ,Tsai TH,Chou SH,Chien CS,Ku HH,Lo JF.Positive correlations of Oct4 and Nanog in oral cancer stem-like cells and high-grade oral squamous cell carcinoma.Clin Cancer Res 2008;14:4085-4095[PMID:18593985 DOI:10.1158/1078-0432.CCR-07-4404]
209 Rentala S,Mangamoori LN.Oct4 expression maintained stem cell properties in prostate cancer-derived cd133 mdr1 cells.Trop J Pharm Res 2009;8:3-9
210 Beltran AS,Rivenbark AG,Richardson BT,Yuan X,Quian H,Hunt JP,Zimmerman E,Graves LM,Blancafort P.Generation of tumor-initiating cells by exogenous delivery of OCT4 transcription factor.Breast Cancer Res 2011;13:R94[PMID:21952072 DOI:10 .1186/bcr3019]
211 Wang YD,Cai N,Wu XL,Cao HZ,Xie LL,Zheng PS.OCT4promotes tumorigenesis and inhibits apoptosis of cervical cancer cells by miR-125b/BAK1 pathway.Cell Death Dis 2013;4:e760[PMID:23928699 DOI:10.1038/cddis.2013.272]
212 Koo BS,Lee SH,Kim JM,Huang S,Kim SH,Rho YS,Bae WJ,Kang HJ,Kim YS,Moon JH,Lim YC.Oct4 is a critical regulator of stemness in head and neck squamous carcinoma cells.Oncogene 2015;34:2317-2324[PMID:24954502 DOI:10.1038/onc.2014.174]
213 Kamachi Y,Uchikawa M,Kondoh H.Pairing SOX off:with partners in the regulation of embryonic development.Trends Genet2000;16:182-187[PMID:10729834]
214 Avilion AA,Nicolis SK,Pevny LH,Perez L,Vivian N,Lovell-Badge R.Multipotent cell lineages in early mouse development depend on SOX2 function.Genes Dev 2003;17:126-140[PMID:12514105 DOI:10.1101/gad.224503]
215 Masui S,Nakatake Y,Toyooka Y,Shimosato D,Yagi R,Takahashi K,Okochi H,Okuda A,Matoba R,Sharov AA,Ko MS,Niwa H.Pluripotency governed by Sox2 via regulation of Oct3/4 expression in mouse embryonic stem cells.Nat Cell Biol 2007;9:625-635[PMID:17515932]
216 Boer B,Kopp J,Mallanna S,Desler M,Chakravarthy H,Wilder PJ,Bernadt C,Rizzino A.Elevating the levels of Sox2 in embryonal carcinoma cells and embryonic stem cells inhibits the expression of Sox2:Oct-3/4 target genes.Nucleic Acids Res 2007;35:1773-1786[PMID:17324942]
217 Kopp JL,Ormsbee BD,Desler M,Rizzino A.Small increases in the level of Sox2 trigger the differentiation of mouse embryonic stem cells.Stem Cells 2008;26:903-911[PMID:18238855 DOI:10 .1634/stemcells.2007-0951]
218 Basu-Roy U,Seo E,Ramanathapuram L,Rapp TB,Perry JA,Orkin SH,Mansukhani A,Basilico C.Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas.Oncogene 2012;31:2270-2282[PMID:21927024 DOI:10.1038/onc.2011.405]
219 Lou X,Han X,Jin C,Tian W,Yu W,Ding D,Cheng L,Huang B,Jiang H,Lin B.SOX2 targets fibronectin 1 to promote cell migration and invasion in ovarian cancer:new molecular leads for therapeutic intervention.OMICS 2013;17:510-518[PMID:23895273 DOI:10.1089/omi.2013.0058]
220 Tian T,Zhang Y,Wang S,Zhou J,Xu S.Sox2 enhances the tumorigenicity and chemoresistance of cancer stem-like cells derived from gastric cancer.J Biomed Res 2012;26:336-345[PMID:23554769 DOI:10.7555/JBR.26.20120045]
221 Herreros-Villanueva M,Zhang JS,Koenig A,Abel EV,Smyrk TC,Bamlet WR,de Narvajas AA,Gomez TS,Simeone DM,Bujanda L,Billadeau DD.SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells.Oncogenesis 2013;2:e61[PMID:23917223 DOI:10.1038/oncsis.2013.23]
222 Rybak AP,Tang D.SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells.Cell Signal 2013;25:2734-2742[PMID:24036214 DOI:10.1016/j.cellsig.2013.08.041]
223 Singh S,Trevino J,Bora-Singhal N,Coppola D,Haura E,Altiok S,Chellappan SP.EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer.Mol Cancer 2012;11:73[PMID:23009336 DOI:10 .1186/1476-4598-11-73]
224 Santini R,Pietrobono S,Pandolfi S,Montagnani V,D’Amico M,Penachioni JY,Vinci MC,Borgognoni L,Stecca B.SOX2 regulates self-renewal and tumorigenicity of human melanoma-initiating cells.Oncogene 2014;33:4697-4708[PMID:24681955 DOI:10 .1038/onc.2014.71]
225 Favaro R,Appolloni I,Pellegatta S,Sanga AB,Pagella P,Gambini E,Pisati F,Ottolenghi S,Foti M,Finocchiaro G,Malatesta P,Nicolis SK.Sox2 is required to maintain cancer stem cells in a mouse model of high-grade oligodendroglioma.Cancer Res 2014;74 :1833-1844[PMID:24599129 DOI:10.1158/0008-5472.CAN-13-1942]
226 Chambers I,Silva J,Colby D,Nichols J,Nijmeijer B,Robertson M,Vrana J,Jones K,Grotewold L,Smith A.Nanog safeguards pluripotency and mediates germline development.Nature 2007;450 :1230-1234[PMID:18097409 DOI:10.1038/nature06403]
227 Mitsui K,Tokuzawa Y,Itoh H,Segawa K,Murakami M,Takahashi K,Maruyama M,Maeda M,Yamanaka S.The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells.Cell 2003;113:631-642[PMID:12787504]
228 Chambers I,Colby D,Robertson M,Nichols J,Lee S,Tweedie S,Smith A.Functional expression cloning of Nanog,a pluripotency sustaining factor in embryonic stem cells.Cell 2003;113:643-655[PMID:12787505]
229 Silva J,Nichols J,Theunissen TW,Guo G,van Oosten AL,Barrandon O,Wray J,Yamanaka S,Chambers I,Smith A.Nanog is the gateway to the pluripotent ground state.Cell 2009;138:722-737[PMID:19703398 DOI:10.1016/j.cell.2009.07.039]
230 Hyslop L,Stojkovic M,Armstrong L,Walter T,Stojkovic P,Przyborski S,Herbert M,Murdoch A,Strachan T,Lako M.Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages.Stem Cells 2005;23:1035-1043[PMID:15983365 DOI:10.1634/stemcells.2005-0080]
231 Kuroda T,Tada M,Kubota H,Kimura H,Hatano SY,Suemori H,Nakatsuji N,Tada T.Octamer and Sox elements are required for transcriptional cis regulation of Nanog gene expression.Mol Cell Biol 2005;25:2475-2485[PMID:15743839 DOI:10.1128/MCB.25.6.2475-2485.2005]
232 Amsterdam A,Raanan C,Schreiber L,Freyhan O,Schechtman L,Givol D.Localization of the stem cell markers LGR5 and Nanog in the normal and the cancerous human ovary and their inter-relationship.Acta Histochem 2013;115:330-338[PMID:23092806DOI:10.1016/j.acthis.2012.09.004]
233 Bussolati B,Bruno S,Grange C,Ferrando U,Camussi G.Identi-fication of a tumor-initiating stem cell population in human renal carcinomas.FASEB J 2008;22:3696-3705[PMID:18614581 DOI:10 .1096/fj.08-102590]
234 Chiou SH,Wang ML,Chou YT,Chen CJ,Hong CF,Hsieh WJ,Chang HT,Chen YS,Lin TW,Hsu HS,Wu CW.Coexpression of Oct4 and Nanog enhances malignancy in lung adenocarcinoma by inducing cancer stem cell-like properties and epithelial-mesenchymal transdifferentiation.Cancer Res 2010;70:10433-10444[PMID:21159654 DOI:10.1158/0008-5472.can-10-2638]
235 Lu X,Mazur SJ,Lin T,Appella E,Xu Y.The pluripotency factor nanog promotes breast cancer tumorigenesis and metastasis.Oncogene 2014;33:2655-2664[PMID:23770853 DOI:10.1038/onc.2013.209]
236 Guo Y,Liu S,Wang P,Zhao S,Wang F,Bing L,Zhang Y,Ling EA,Gao J,Hao A.Expression profile of embryonic stem cell-associated genes Oct4,Sox2 and Nanog in human gliomas.Histopathology 2011;59:763-775[PMID:22014056 DOI:10.1111/j.1365-2559.2011.03993.x]
237 Lin T,Ding YQ,Li JM.Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma.Med Oncol 2012;29:878-885[PMID:21336986 DOI:10.1007/s12032-011-9860-9]
238 Lee M,Nam EJ,Kim SW,Kim S,Kim JH,Kim YT.Prognostic impact of the cancer stem cell-related marker NANOG in ovarian serous carcinoma.Int J Gynecol Cancer 2012;22:1489-1496[PMID:23095773 DOI:10.1097/IGJ.0b013e3182738307]
239 Meng HM,Zheng P,Wang XY,Liu C,Sui HM,Wu SJ,Zhou J,Ding YQ,Li J.Over-expression of Nanog predicts tumor progression and poor prognosis in colorectal cancer.Cancer Biol Ther 2010;9:295-302[PMID:20026903 DOI:10.4161/cbt.9.4.10666]
240 Nagata T,Shimada Y,Sekine S,Hori R,Matsui K,Okumura T,Sawada S,Fukuoka J,Tsukada K.Prognostic significance of NANOG and KLF4 for breast cancer.Breast Cancer 2014;21:96 -101[PMID:22528804 DOI:10.1007/s12282-012-0357-y]
241 Ibrahim EE,Babaei-Jadidi R,Saadeddin A,Spencer-Dene B,Hossaini S,Abuzinadah M,Li N,Fadhil W,Ilyas M,Bonnet D,Nateri AS.Embryonic NANOG activity defines colorectal cancer stem cells and modulates through AP1-and TCF-dependent mechanisms.Stem Cells 2012;30:2076-2087[PMID:22851508DOI:10.1002/stem.1182]
242 Jeter CR,Liu B,Liu X,Chen X,Liu C,Calhoun-Davis T,Repass J,Zaehres H,Shen JJ,Tang DG.NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation.Oncogene 2011;30:3833-3845[PMID:21499299DOI:10.1038/onc.2011.114]
243 Lee TK,Castilho A,Cheung VC,Tang KH,Ma S,Ng IO.CD24(+)liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation.Cell Stem Cell 2011;9 :50-63[PMID:21726833 DOI:10.1016/j.stem.2011.06.005]
244 Niu CS,Li DX,Liu YH,Fu XM,Tang SF,Li J.Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells.Oncol Rep 2011;26:593-601[PMID:21573506 DOI:10 .3892/or.2011.1308]
245 Zbinden M,Duquet A,Lorente-Trigos A,Ngwabyt SN,Borges I,Ruiz i Altaba A.NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1and p53.EMBO J 2010;29:2659-2674[PMID:20581802 DOI:10 .1038/emboj.2010.137]
246 Zhou X,Zhou YP,Huang GR,Gong BL,Yang B,Zhang DX,Hu P,Xu SR.Expression of the stem cell marker,Nanog,in human endometrial adenocarcinoma.Int J Gynecol Pathol 2011;30:262 -270[PMID:21464727 DOI:10.1097/PGP.0b013e3182055a1f]
247 Wang ML,Chiou SH,Wu CW.Targeting cancer stem cells:emerging role of Nanog transcription factor.Onco Targets Ther2013;6:1207-1220[PMID:24043946 DOI:10.2147/OTT.S38114]
248 He A,Qi W,Huang Y,Feng T,Chen J,Sun Y,Shen Z,Yao Y.CD133 expression predicts lung metastasis and poor prognosis in osteosarcoma patients:A clinical and experimental study.Exp Ther Med 2012;4:435-441[PMID:23181114 DOI:10.3892/etm.2012.603]
249 Leung EL,Fiscus RR,Tung JW,Tin VP,Cheng LC,Sihoe AD,Fink LM,Ma Y,Wong MP.Non-small cell lung cancer cells expressing CD44 are enriched for stem cell-like properties.PLoS One 2010;5:e14062[PMID:21124918 DOI:10.1371/journal.pone.0014062]
250 Han J,Zhang F,Yu M,Zhao P,Ji W,Zhang H,Wu B,Wang Y,Niu R.RNA interference-mediated silencing of NANOG reduces cell proliferation and induces G0/G1 cell cycle arrest in breast cancer cells.Cancer Lett 2012;321:80-88[PMID:22381696 DOI:10 .1016/j.canlet.2012.02.021]
251 Siu MK,Wong ES,Kong DS,Chan HY,Jiang L,Wong OG,Lam EW,Chan KK,Ngan HY,Le XF,Cheung AN.Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and Fox J1 and contributes to adverse clinical outcome in ovarian cancers.Oncogene 2013;32:3500-3509[PMID:22945654 DOI:10.1038/onc.2012.363]
252 Bourillot PY,Aksoy I,Schreiber V,Wianny F,Schulz H,Hummel O,Hubner N,Savatier P.Novel STAT3 target genes exert distinct roles in the inhibition of mesoderm and endoderm differentiation in cooperation with Nanog.Stem Cells 2009;27:1760-1771[PMID:19544440 DOI:10.1002/stem.110]
253 Ghaleb AM,Nandan MO,Chanchevalap S,Dalton WB,Hisamuddin IM,Yang VW.Krüppel-like factors 4 and 5:the yin and yang regulators of cellular proliferation.Cell Res 2005;15:92 -96[PMID:15740636]
254 Bourillot PY,Savatier P.Krüppel-like transcription factors and control of pluripotency.BMC Biol 2010;8:125[PMID:20875146DOI:10.1186/1741-7007-8-125]
255 Ivanova N,Dobrin R,Lu R,Kotenko I,Levorse J,De Coste C,Schafer X,Lun Y,Lemischka IR.Dissecting self-renewal in stem cells with RNA interference.Nature 2006;442:533-538[PMID:16767105]
256 Li Y,Mc Clintick J,Zhong L,Edenberg HJ,Yoder MC,Chan RJ.Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4.Blood 2005;105:635-637[PMID:15358627 DOI:10.1182/blood-2004-07-2681]
257 Nakatake Y,Fukui N,Iwamatsu Y,Masui S,Takahashi K,Yagi R,Yagi K,Miyazaki J,Matoba R,Ko MS,Niwa H.Klf4 cooperates with Oct3/4 and Sox2 to activate the Lefty1 core promoter in embryonic stem cells.Mol Cell Biol 2006;26:7772-7782[PMID:16954384 DOI:10.1128/MCB.00468-06]
258 Jiang J,Chan YS,Loh YH,Cai J,Tong GQ,Lim CA,Robson P,Zhong S,Ng HH.A core Klf circuitry regulates self-renewal of embryonic stem cells.Nat Cell Biol 2008;10:353-360[PMID:18264089 DOI:10.1038/ncb1698]
259 Yasunaga M,Tada S,Torikai-Nishikawa S,Nakano Y,Okada M,Jakt LM,Nishikawa S,Chiba T,Era T,Nishikawa S.Induction and monitoring of definitive and visceral endoderm differentiation of mouse ES cells.Nat Biotechnol 2005;23:1542-1550[PMID:16311587 DOI:10.1038/nbt1167]
260 Aksoy I,Giudice V,Delahaye E,Wianny F,Aubry M,Mure M,Chen J,Jauch R,Bogu GK,Nolden T,Himmelbauer H,Xavier Doss M,Sachinidis A,Schulz H,Hummel O,Martinelli P,Hübner N,Stanton LW,Real FX,Bourillot PY,Savatier P.Klf4 and Klf5differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells.Nat Commun 2014;5:3719[PMID:24770696 DOI:10.1038/ncomms4719]
261 Wong CW,Hou PS,Tseng SF,Chien CL,Wu KJ,Chen HF,Ho HN,Kyo S,Teng SC.Krüppel-like transcription factor 4 contributes to maintenance of telomerase activity in stem cells.Stem Cells2010;28:1510-1517[PMID:20629177 DOI:10.1002/stem.477]
262 Hoffmeyer K,Raggioli A,Rudloff S,Anton R,Hierholzer A,Del Valle I,Hein K,Vogt R,Kemler R.Wnt/β-catenin signaling regulates telomerase in stem cells and cancer cells.Science 2012;336 :1549-1554[PMID:22723415 DOI:10.1126/science.1218370]
263 Yu F,Li J,Chen H,Fu J,Ray S,Huang S,Zheng H,Ai W.Kruppel-like factor 4(KLF4)is required for maintenance of breast cancer stem cells and for cell migration and invasion.Oncogene 2011;30:2161-2172[PMID:21242971 DOI:10.1038/onc.2010.591]
264 Yu T,Chen X,Zhang W,Li J,Xu R,Wang TC,Ai W,Liu C.Krüppel-like factor 4 regulates intestinal epithelial cell morphology and polarity.PLoS One 2012;7:e32492[PMID:22384261 DOI:10 .1371/journal.pone.0032492]
265 Yori JL,Johnson E,Zhou G,Jain MK,Keri RA.Kruppel-like factor 4 inhibits epithelial-to-mesenchymal transition through regulation of E-cadherin gene expression.J Biol Chem 2010;285:16854-16863[PMID:20356845 DOI:10.1074/jbc.M110.114546]
266 Leng Z,Tao K,Xia Q,Tan J,Yue Z,Chen J,Xi H,Li J,Zheng H.Krüppel-like factor 4 acts as an oncogene in colon cancer stem cell-enriched spheroid cells.PLo S One 2013;8:e56082[PMID:23418515 DOI:10.1371/journal.pone.0056082]
267 Wellner U,Schubert J,Burk UC,Schmalhofer O,Zhu F,Sonntag A,Waldvogel B,Vannier C,Darling D,zur Hausen A,Brunton VG,Morton J,Sansom O,Schüler J,Stemmler MP,Herzberger C,Hopt U,Keck T,Brabletz S,Brabletz T.The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microR NAs.Nat Cell Biol 2009;11:1487-1495[PMID:19935649DOI:10.1038/ncb1998]
268 Okuda H,Xing F,Pandey PR,Sharma S,Watabe M,Pai SK,Mo YY,Iiizumi-Gairani M,Hirota S,Liu Y,Wu K,Pochampally R,Watabe K.miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4.Cancer Res 2013;73:1434-1444[PMID:23384942 DOI:10.1158/0008-5472.CAN-12-2037]
269 Ma J,Yao Y,Wang P,Liu Y,Zhao L,Li Z,Li Z,Xue Y.MiR-152functions as a tumor suppressor in glioblastoma stem cells by targeting Krüppel-like factor 4.Cancer Lett 2014;355:85-95[PMID:25218589 DOI:10.1016/j.canlet.2014.09.012]
270 Cole MD,Henriksson M.25 years of the c-Myc oncogene.Semin Cancer Biol 2006;16:241[PMID:16935523]
271 Laurenti E,Wilson A,Trumpp A.Myc’s other life:stem cells and beyond.Curr Opin Cell Biol 2009;21:844-854[PMID:19836223DOI:10.1016/j.ceb.2009.09.006]
272 Meyer N,Kim SS,Penn LZ.The Oscar-worthy role of Myc in apoptosis.Semin Cancer Biol 2006;16:275-287[PMID:16945552]
273 Cartwright P,McL ean C,Sheppard A,Rivett D,Jones K,Dalton S.LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism.Development 2005;132:885-896[PMID:15673569]
274 Smith KN,Singh AM,Dalton S.Myc represses primitive endoderm differentiation in pluripotent stem cells.Cell Stem Cell 2010;7:343 -354[PMID:20804970 DOI:10.1016/j.stem.2010.06.023]
275 Chappell J,Sun Y,Singh A,Dalton S.MYC/MAX control ERK signaling and pluripotency by regulation of dual-specificity phosphatases 2 and 7.Genes Dev 2013;27:725-733[PMID:23592794 DOI:10.1101/gad.211300.112]
276 Kidder BL,Yang J,Palmer S.Stat3 and c-Myc genome-wide promoter occupancy in embryonic stem cells.PLoS One 2008;3:e3932[PMID:19079543 DOI:10.1371/journal.pone.0003932]
277 Kim J,Chu J,Shen X,Wang J,Orkin SH.An extended transcriptional network for pluripotency of embryonic stem cells.Cell 2008;132:1049-1061[PMID:18358816 DOI:10.1016/j.cell.2008.02.039]
278 Sridharan R,Tchieu J,Mason MJ,Yachechko R,Kuoy E,Horvath S,Zhou Q,Plath K.Role of the murine reprogramming factors in the induction of pluripotency.Cell 2009;136:364-377[PMID:19167336 DOI:10.1016/j.cell.2009.01.001]
279 Yin XY,Grove L,Datta NS,Katula K,Long MW,Prochownik EV.Inverse regulation of cyclin B1 by c-Myc and p53 and induction of tetraploidy by cyclin B1 overexpression.Cancer Res 2001;61:6487-6493[PMID:11522645]
280 Eilers M,Eisenman RN.Myc’s broad reach.Genes Dev 2008;22:2755-2766[PMID:18923074 DOI:10.1101/gad.1712408]
281 Zheng H,Ying H,Yan H,Kimmelman AC,Hiller DJ,Chen AJ,Perry SR,Tonon G,Chu GC,Ding Z,Stommel JM,Dunn KL,Wiedemeyer R,You MJ,Brennan C,Wang YA,Ligon KL,Wong WH,Chin L,de Pinho RA.Pten and p53 converge on c-Myc to control differentiation,self-renewal,and transformation of normal and neoplastic stem cells in glioblastoma.Cold Spring Harb Symp Quant Biol 2008;73:427-437[PMID:19150964 DOI:10.1101/sqb.2008.73.047]
282 Ho C,Wang C,Mattu S,Destefanis G,Ladu S,Delogu S,Armbruster J,Fan L,Lee SA,Jiang L,Dombrowski F,Evert M,Chen X,Calvisi DF.AKT(v-akt murine thymoma viral oncogene homolog 1)and N-Ras(neuroblastoma ras viral oncogene homolog)coactivation in the mouse liver promotes rapid carcinogenesis by way of m TOR(mammalian target of rapamycin complex 1 ),FOXM1(forkhead box M1)/SKP2,and c-Myc pathways.Hepatology 2012;55:833-845[PMID:21993994 DOI:10.1002/hep.24736]
283 Wang J,Wang H,Li Z,Wu Q,Lathia JD,Mc Lendon RE,Hjelmeland AB,Rich JN.c-Myc is required for maintenance of glioma cancer stem cells.PLo S One 2008;3:e3769[PMID:19020659 DOI:10.1371/journal.pone.0003769]
284 Salcido CD,Larochelle A,Taylor BJ,Dunbar CE,Varticovski L.Molecular characterisation of side population cells with cancer stem cell-like characteristics in small-cell lung cancer.Br J Cancer 2010;102 :1636-1644[PMID:20424609 DOI:10.1038/sj.bjc.6605668]
285 Walter D,Satheesha S,Albrecht P,Bornhauser BC,D’Alessandro V,Oesch SM,Rehrauer H,Leuschner I,Koscielniak E,Gengler C,Moch H,Bernasconi M,Niggli FK,Sch?fer BW.CD133 positive embryonal rhabdomyosarcoma stem-like cell population is enriched in rhabdospheres.PLo S One 2011;6:e19506[PMID:21602936DOI:10.1371/journal.pone.0019506]
286 Civenni G,Malek A,Albino D,Garcia-Escudero R,Napoli S,Di Marco S,Pinton S,Sarti M,Carbone GM,Catapano CV.RNAi-mediated silencing of Myc transcription inhibits stem-like cell maintenance and tumorigenicity in prostate cancer.Cancer Res2013;73:6816-6827[PMID:24063893 DOI:10.1158/0008-5472.CAN-13-0615]
287 Akita H,Marquardt JU,Durkin ME,Kitade M,Seo D,Conner EA,Andersen JB,Factor VM,Thorgeirsson SS.MYC activates stem-like cell potential in hepatocarcinoma by a p53-dependent mechanism.Cancer Res 2014;74:5903-5913[PMID:25189530]
288 Hitchler MJ,Rice JC.Genome-wide epigenetic analysis of human pluripotent stem cells by Ch IP and Ch IP-Seq.Methods Mol Biol2011;767:253-267[PMID:21822881 DOI:10.1007/978-1-61779- 201 -4_19]
289 Revill K,Wang T,Lachenmayer A,Kojima K,Harrington A,Li J,Hoshida Y,Llovet JM,Powers S.Genome-wide methylation analysis and epigenetic unmasking identify tumor suppressor genes in hepatocellular carcinoma.Gastroenterology 2013;145:1424-35.e1-25[PMID:24012984 DOI:10.1053/j.gastro.2013.08.055]
290 Jurkowska RZ,Jurkowski TP,Jeltsch A.Structure and function of mammalian DNA methyltransferases.Chembiochem 2011;12:206 -222[PMID:21243710 DOI:10.1002/cbic.201000195]
291 Fatemi M,Hermann A,Gowher H,Jeltsch A.Dnmt3a and Dnmt1functionally cooperate during de novo methylation of DNA.Eur J Biochem 2002;269:4981-4984[PMID:12383256]
292 Walton EL,Francastel C,Velasco G.Maintenance of DNA methylation:Dnmt3b joins the dance.Epigenetics 2011;6:1373-1377[PMID:22048250 DOI:10.4161/epi.6.11.17978]
293 Jackson M,Krassowska A,Gilbert N,Chevassut T,Forrester L,Ansell J,Ramsahoye B.Severe global DNA hypomethylation blocks differentiation and induces histone hyperacetylation in embryonic stem cells.Mol Cell Biol 2004;24:8862-8871[PMID:15456861 DOI:10.1128/MCB.24.20.8862-8871.2004]
294 Zvetkova I,Apedaile A,Ramsahoye B,Mermoud JE,Crompton LA,John R,Feil R,Brockdorff N.Global hypomethylation of the genome in XX embryonic stem cells.Nat Genet 2005;37:1274-1279[PMID:16244654 DOI:10.1038/ng1663]
295 Fouse SD,Shen Y,Pellegrini M,Cole S,Meissner A,Van Neste L,Jaenisch R,Fan G.Promoter Cp G methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog,PcG complex,and histone H3 K4/K27 trimethylation.Cell Stem Cell 2008;2:160-169[PMID:18371437 DOI:10.1016/j.stem.2007.12.011]
296 Bibikova M,Chudin E,Wu B,Zhou L,Garcia EW,Liu Y,Shin S,Plaia TW,Auerbach JM,Arking DE,Gonzalez R,Crook J,Davidson B,Schulz TC,Robins A,Khanna A,Sartipy P,Hyllner J,Vanguri P,Savant-Bhonsale S,Smith AK,Chakravarti A,Maitra A,Rao M,Barker DL,Loring JF,Fan JB.Human embryonic stem cells have a unique epigenetic signature.Genome Res 2006;16:1075-1083[PMID:16899657 DOI:10.1101/gr.5319906]
297 Lister R,Pelizzola M,Dowen RH,Hawkins RD,Hon G,Tonti-Filippini J,Nery JR,Lee L,Ye Z,Ngo QM,Edsall L,Antosiewicz-Bourget J,Stewart R,Ruotti V,Millar AH,Thomson JA,Ren B,Ecker JR.Human DNA methylomes at base resolution show widespread epigenomic differences.Nature 2009;462:315-322[PMID:19829295 DOI:10.1038/nature08514]
298 Laurent L,Wong E,Li G,Huynh T,Tsirigos A,Ong CT,Low HM,Kin Sung KW,Rigoutsos I,Loring J,Wei CL.Dynamic changes in the human methylome during differentiation.Genome Res 2010;20 :320-331[PMID:20133333 DOI:10.1101/gr.101907.109]
299 Zhao L,Sun MA,Li Z,Bai X,Yu M,Wang M,Liang L,Shao X,Arnovitz S,Wang Q,He C,Lu X,Chen J,Xie H.The dynamics of DNA methylation fidelity during mouse embryonic stem cell selfrenewal and differentiation.Genome Res 2014;24:1296-1307[PMID:24835587 DOI:10.1101/gr.163147.113]
300 Arand J,Spieler D,Karius T,Branco MR,Meilinger D,Meissner A,Jenuwein T,Xu G,Leonhardt H,Wolf V,Walter J.In vivo control of CpG and non-CpG DNA methylation by DNA methyltransferases.PLoS Genet 2012;8:e1002750[PMID:22761581 DOI:10.1371/journal.pgen.1002750]
301 Ziller MJ,Müller F,Liao J,Zhang Y,Gu H,Bock C,Boyle P,Epstein CB,Bernstein BE,Lengauer T,Gnirke A,Meissner A.Genomic distribution and inter-sample variation of non-Cp G methylation across human cell types.PLo S Genet 2011;7:e1002389[PMID:22174693 DOI:10.1371/journal.pgen.1002389]
302 Li E,Bestor TH,Jaenisch R.Targeted mutation of the DNA methyltransferase gene results in embryonic lethality.Cell 1992;69:915 -926[PMID:1606615]
303 Okano M,Bell DW,Haber DA,Li E.DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.Cell 1999;99:247-257[PMID:10555141]
304 Biniszkiewicz D,Gribnau J,Ramsahoye B,Gaudet F,Eggan K,Humpherys D,Mastrangelo MA,Jun Z,Walter J,Jaenisch R.Dnmt1 overexpression causes genomic hypermethylation,loss of imprinting,and embryonic lethality.Mol Cell Biol 2002;22:2124-2135[PMID:11884600]
305 Robertson KD,Uzvolgyi E,Liang G,Talmadge C,Sumegi J,Gonzales FA,Jones PA.The human DNA methyltransferases(DNMTs)1,3a and 3b:coordinate m RNA expression in normal tissues and overexpression in tumors.Nucleic Acids Res 1999;27:2291-2298[PMID:10325416]
306 Pawlak M,Jaenisch R.De novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells to a pluripotent state.Genes Dev 2011;25:1035-1040[PMID:21576263 DOI:10.1101/gad.2039011]
307 Tahiliani M,Koh KP,Shen Y,Pastor WA,Bandukwala H,Brudno Y,Agarwal S,Iyer LM,Liu DR,Aravind L,Rao A.Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1.Science 2009;324:930-935[PMID:19372391 DOI:10.1126/science.1170116]
308 Ito S,D’Alessio AC,Taranova OV,Hong K,Sowers LC,Zhang Y.Role of Tet proteins in 5mC to 5hmC conversion,ES-cell self-renewal and inner cell mass specification.Nature 2010;466:1129-1133[PMID:20639862 DOI:10.1038/nature09303]
309 He YF,Li BZ,Li Z,Liu P,Wang Y,Tang Q,Ding J,Jia Y,Chen Z,Li L,Sun Y,Li X,Dai Q,Song CX,Zhang K,He C,Xu GL.Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.Science 2011;333:1303-1307[PMID:21817016 DOI:10.1126/science.1210944]
310 Ito S,Shen L,Dai Q,Wu SC,Collins LB,Swenberg JA,He C,Zhang Y.Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5 -carboxylcytosine.Science 2011;333:1300-1303[PMID:21778364DOI:10.1126/science.1210597]
311 Globisch D,Münzel M,Müller M,Michalakis S,Wagner M,Koch S,Brückl T,Biel M,Carell T.Tissue distribution of 5 -hydroxymethylcytosine and search for active demethylation intermediates.PLoS One 2010;5:e15367[PMID:21203455 DOI:10 .1371/journal.pone.0015367]
312 Stroud H,Feng S,Morey Kinney S,Pradhan S,Jacobsen SE.5 -Hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells.Genome Biol 2011;12:R54[PMID:21689397 DOI:10.1186/gb-2011-12-6-r54]
313 Ficz G,Branco MR,Seisenberger S,Santos F,Krueger F,Hore TA,Marques CJ,Andrews S,Reik W.Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation.Nature 2011;473:398-402[PMID:21460836 DOI:10 .1038/nature10008]
314 Robertson J,Robertson AB,Klungland A.The presence of 5 -hydroxymethylcytosine at the gene promoter and not in the gene body negatively regulates gene expression.Biochem Biophys Res Commun 2011;411:40-43[PMID:21703242 DOI:10.1016/j.bbrc.2011.06.077]
315 Koh KP,Yabuuchi A,Rao S,Huang Y,Cunniff K,Nardone J,Laiho A,Tahiliani M,Sommer CA,Mostoslavsky G,Lahesmaa R,Orkin SH,Rodig SJ,Daley GQ,Rao A.Tet1 and Tet2 regulate 5 -hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells.Cell Stem Cell 2011;8:200-213[PMID:21295276 DOI:10.1016/j.stem.2011.01.008]
316 Huang Y,Chavez L,Chang X,Wang X,Pastor WA,Kang J,Zepeda-Martínez JA,Pape UJ,Jacobsen SE,Peters B,Rao A.Distinct roles of the methylcytosine oxidases Tet1 and Tet2 in mouse embryonic stem cells.Proc Natl Acad Sci USA 2014;111:1361-1366[PMID:24474761 DOI:10.1073/pnas.1322921111]
317 Wu H,Zhang Y.Tet1 and 5-hydroxymethylation:a genome-wide view in mouse embryonic stem cells.Cell Cycle 2011;10:2428-2436[PMID:21750410]
318 Williams K,Christensen J,Pedersen MT,Johansen JV,Cloos PA,Rappsilber J,Helin K.TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.Nature 2011;473:343 -348[PMID:21490601 DOI:10.1038/nature10066]
319 Vella P,Scelfo A,Jammula S,Chiacchiera F,Williams K,Cuomo A,Roberto A,Christensen J,Bonaldi T,Helin K,Pasini D.Tet proteins connect the O-linked N-acetylglucosamine transferase Ogt to chromatin in embryonic stem cells.Mol Cell 2013;49:645-656[PMID:23352454 DOI:10.1016/j.molcel.2012.12.019]
320 Shi FT,Kim H,Lu W,He Q,Liu D,Goodell MA,Wan M,Songyang Z.Ten-eleven translocation 1(Tet1)is regulated by O-linked N-acetylglucosamine transferase(Ogt)for target gene repression in mouse embryonic stem cells.J Biol Chem 2013;288:20776-20784[PMID:23729667 DOI:10.1074/jbc.M113.460386]
321 Freudenberg JM,Ghosh S,Lackford BL,Yellaboina S,Zheng X,Li R,Cuddapah S,Wade PA,Hu G,Jothi R.Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3signaling and results in loss of embryonic stem cell identity.Nucleic Acids Res 2012;40:3364-3377[PMID:22210859 DOI:10.1093/nar/gkr1253]
322 Dawlaty MM,Breiling A,Le T,Barrasa MI,Raddatz G,Gao Q,Powell BE,Cheng AW,Faull KF,Lyko F,Jaenisch R.Loss of Tet enzymes compromises proper differentiation of embryonic stem cells.Dev Cell 2014;29:102-111[PMID:24735881 DOI:10.1016/j.devcel.2014.03.003]
323 Dumitrescu RG,Verma M.Cancer epigenetics:Methods and protocols.Totowa NJ:Humana.London:Springer[distributor],2012
324 Esteller M.Epigenetics in cancer.N Engl J Med 2008;358:1148-1159[PMID:18337604 DOI:10.1056/NEJMra072067358/11/1148]
325 Feinberg AP,Ohlsson R,Henikoff S.The epigenetic progenitor origin of human cancer.Nat Rev Genet 2006;7:21-33[PMID:16369569]
326 Nishigaki M,Aoyagi K,Danjoh I,Fukaya M,Yanagihara K,Sakamoto H,Yoshida T,Sasaki H.Discovery of aberrant expression of R-RAS by cancer-linked DNA hypomethylation in gastric cancer using microarrays.Cancer Res 2005;65:2115-2124[PMID:15781621]
327 Nakamura M,Yonekawa Y,Kleihues P,Ohgaki H.Promoter hypermethylation of the RB1 gene in glioblastomas.Lab Invest2001;81:77-82[PMID:11204276]
328 Lahtz C,Pfeifer GP.Epigenetic changes of DNA repair genes in cancer.J Mol Cell Biol 2011;3:51-58[PMID:21278452 DOI:10 .1093/jmcb/mjq053]
329 Yasuda H,Soejima K,Watanabe H,Kawada I,Nakachi I,Yoda S,Nakayama S,Satomi R,Ikemura S,Terai H,Sato T,Suzuki S,Matsuzaki Y,Naoki K,Ishizaka A.Distinct epigenetic regulation of tumor suppressor genes in putative cancer stem cells of solid tumors.Int J Oncol 2010;37:1537-1546[PMID:21042723]
330 Ikegaki N,Shimada H,Fox AM,Regan PL,Jacobs JR,Hicks SL,Rappaport EF,Tang XX.Transient treatment with epigenetic modifiers yields stable neuroblastoma stem cells resembling aggressive large-cell neuroblastomas.Proc Natl Acad Sci USA 2013;110 :6097-6102[PMID:23479628 DOI:10.1073/pnas.1118262110]
331 Patra SK,Patra A,Zhao H,Dahiya R.DNA methyltransferase and demethylase in human prostate cancer.Mol Carcinog 2002;33:163 -171[PMID:11870882 DOI:10.1002/mc.10033]
332 Oh BK,Kim H,Park HJ,Shim YH,Choi J,Park C,Park YN.DNA methyltransferase expression and DNA methylation in human hepatocellular carcinoma and their clinicopathological correlation.Int J Mol Med 2007;20:65-73[PMID:17549390]
333 Melki JR,Warnecke P,Vincent PC,Clark SJ.Increased DNA methyltransferase expression in leukaemia.Leukemia 1998;12:311 -316[PMID:9529124]
334 Wu J,Issa JP,Herman J,Bassett DE,Nelkin BD,Baylin SB.Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of NIH 3T3 cells.Proc Natl Acad Sci USA 1993;90:8891-8895[PMID:8415627]
335 MacL eod AR,Szyf M.Expression of antisense to DNA methylt-ransferase m RNA induces DNA demethylation and inhibits tumorigenesis.J Biol Chem 1995;270:8037-8043[PMID:7713905]
336 Morita R,Hirohashi Y,Suzuki H,Takahashi A,Tamura Y,Kanaseki T,Asanuma H,Inoda S,Kondo T,Hashino S,Hasegawa T,Tokino T,Toyota M,Asaka M,Torigoe T,Sato N.DNA methyltransferase 1is essential for initiation of the colon cancers.Exp Mol Pathol 2013;94 :322-329[PMID:23064049 DOI:10.1016/j.yexmp.2012.10.004]
337 Trowbridge JJ,Sinha AU,Zhu N,Li M,Armstrong SA,Orkin SH.Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through derepression of bivalent chromatin domains.Genes Dev 2012;26:344-349[PMID:22345515 DOI:10.1101/gad.184341.111]
338 Choi DS,Blanco E,Kim YS,Rodriguez AA,Zhao H,Huang TH,Chen CL,Jin G,Landis MD,Burey LA,Qian W,Granados SM,Dave B,Wong HH,Ferrari M,Wong ST,Chang JC.Chloroquine eliminates cancer stem cells through deregulation of Jak2 and DNMT1.Stem Cells 2014;32:2309-2323[PMID:24809620 DOI:10 .1002/stem.1746]
339 Mariani CJ,Madzo J,Moen EL,Yesilkanal A,Godley LA.Alterations of 5-hydroxymethylcytosine in human cancers.Cancers(Basel)2013;5:786-814[PMID:24202321 DOI:10.3390/cancers5030786]
340 Lorsbach RB,Moore J,Mathew S,Raimondi SC,Mukatira ST,Downing JR.TET1,a member of a novel protein family,is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23).Leukemia 2003;17:637-641[PMID:12646957 DOI:10.1038/sj.leu.2402834]
341 Ono R,Taki T,Taketani T,Taniwaki M,Kobayashi H,Hayashi Y.LCX,leukemia-associated protein with a CXXC domain,is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23).Cancer Res 2002;62:4075-4080[PMID:12124344]
342 Abdel-Wahab O,Mullally A,Hedvat C,Garcia-Manero G,Patel J,Wadleigh M,Malinge S,Yao J,Kilpivaara O,Bhat R,Huberman K,Thomas S,Dolgalev I,Heguy A,Paietta E,Le Beau MM,Beran M,Tallman MS,Ebert BL,Kantarjian HM,Stone RM,Gilliland DG,Crispino JD,Levine RL.Genetic characterization of TET1,TET2,and TET3 alterations in myeloid malignancies.Blood 2009;114:144 -147[PMID:19420352 DOI:10.1182/blood-2009-03-210039]
343 Tsai YP,Chen HF,Chen SY,Cheng WC,Wang HW,Shen ZJ,Song C,Teng SC,He C,Wu KJ.TET1 regulates hypoxia-induced epithelial-mesenchymal transition by acting as a co-activator.Genome Biol 2014;15:513[PMID:25517638 DOI:10.1186/s13059-014-0513-0]
344 Song SJ,Poliseno L,Song MS,Ala U,Webster K,Ng C,Beringer G,Brikbak NJ,Yuan X,Cantley LC,Richardson AL,Pandolfi PP.Micro RNA-antagonism regulates breast cancer stemness and metastasis via TET-family-dependent chromatin remodeling.Cell 2013;154:311-324[PMID:23830207 DOI:10.1016/j.cell.2013.06.026]
345 Plimack ER,Stewart DJ,Issa JP.Combining epigenetic and cytotoxic therapy in the treatment of solid tumors.J Clin Oncol 2007;25:4519-4521[PMID:17925545 DOI:10.1200/JCO.2007.12.6029]
346 Cortez CC,Jones PA.Chromatin,cancer and drug therapies.Mutat Res 2008;647:44-51[PMID:18691602 DOI:10.1016/j.mrfmmm.2008.07.006]
347 Cedar H,Bergman Y.Linking DNA methylation and histone modification:patterns and paradigms.Nat Rev Genet 2009;10:295 -304[PMID:19308066]
348 Haberland M,Montgomery RL,Olson EN.The many roles of histone deacetylases in development and physiology:implications for disease and therapy.Nat Rev Genet 2009;10:32-42[PMID:19065135 DOI:10.1038/nrg2485]
349 Shi Y,Whetstine JR.Dynamic regulation of histone lysine methylation by demethylases.Mol Cell 2007;25:1-14[PMID:17218267 DOI:10.1016/j.molcel.2006.12.010]
350 Azuara V,Perry P,Sauer S,Spivakov M,J?rgensen HF,John RM,Gouti M,Casanova M,Warnes G,Merkenschlager M,Fisher AG.Chromatin signatures of pluripotent cell lines.Nat Cell Biol 2006;8:532 -538[PMID:16570078 DOI:10.1038/ncb1403]
351 Meshorer E,Misteli T.Chromatin in pluripotent embryonic stem cells and differentiation.Nat Rev Mol Cell Biol 2006;7:540-546[PMID:16723974 DOI:10.1038/nrm1938]
352 Bernstein BE,Mikkelsen TS,Xie X,Kamal M,Huebert DJ,Cuff J,Fry B,Meissner A,Wernig M,Plath K,Jaenisch R,Wagschal A,Feil R,Schreiber SL,Lander ES.A bivalent chromatin structure marks key developmental genes in embryonic stem cells.Cell 2006;125 :315-326[PMID:16630819 DOI:10.1016/j.cell.2006.02.041]
353 Voigt P,Tee WW,Reinberg D.A double take on bivalent promoters.Genes Dev 2013;27:1318-1338[PMID:23788621 DOI:10.1101/gad.219626.113]
354 Denissov S,Hofemeister H,Marks H,Kranz A,Ciotta G,Singh S,Anastassiadis K,Stunnenberg HG,Stewart AF.Mll2 is required for H3K4 trimethylation on bivalent promoters in embryonic stem cells,whereas Mll1 is redundant.Development 2014;141:526-537[PMID:24423662 DOI:10.1242/dev.102681]
355 Margueron R,Reinberg D.The Polycomb complex PRC2 and its mark in life.Nature 2011;469:343-349[PMID:21248841 DOI:10 .1038/nature09784]
356 Young MD,Willson TA,Wakefield MJ,Trounson E,Hilton DJ,Blewitt ME,Oshlack A,Majewski IJ.Ch IP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity.Nucleic Acids Res 2011;39:7415-7427[PMID:21652639DOI:10.1093/nar/gkr416]
357 Laugesen A,Helin K.Chromatin repressive complexes in stem cells,development,and cancer.Cell Stem Cell 2014;14:735-751[PMID:24905164 DOI:10.1016/j.stem.2014.05.006]
358 Gil J,O’Loghlen A.PRC1 complex diversity:where is it taking us?Trends Cell Biol 2014;24:632-641[PMID:25065329 DOI:10 .1016/j.tcb.2014.06.005]
359 Faust C,Schumacher A,Holdener B,Magnuson T.The eed mutation disrupts anterior mesoderm production in mice.Development 1995;121:273-285[PMID:7768172]
360 Chamberlain SJ,Yee D,Magnuson T.Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency.Stem Cells 2008;26:1496-1505[PMID:18403752DOI:10.1634/stemcells.2008-0102]
361 Montgomery ND,Yee D,Chen A,Kalantry S,Chamberlain SJ,Otte AP,Magnuson T.The murine polycomb group protein Eed is required for global histone H3 lysine-27 methylation.Curr Biol 2005;15:942-947[PMID:15916951 DOI:10.1016/j.cub.2005.04.051]
362 Pasini D,Bracken AP,Hansen JB,Capillo M,Helin K.The polycomb group protein Suz12 is required for embryonic stem cell differentiation.Mol Cell Biol 2007;27:3769-3779[PMID:17339329 DOI:10.1128/MCB.01432-06]
363 Shen X,Liu Y,Hsu YJ,Fujiwara Y,Kim J,Mao X,Yuan GC,Orkin SH.EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency.Mol Cell 2008;32:491-502[PMID:19026780 DOI:10 .1016/j.molcel.2008.10.016]
364 Akasaka T,van Lohuizen M,van der Lugt N,Mizutani-Koseki Y,Kanno M,Taniguchi M,Vidal M,Alkema M,Berns A,Koseki H.Mice doubly deficient for the Polycomb Group genes Mel18and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression.Development 2001;128:1587-1597[PMID:11290297]
365 Leeb M,Wutz A.Ring1B is crucial for the regulation of developmental control genes and PRC1 proteins but not X inactivation in embryonic cells.J Cell Biol 2007;178:219-229[PMID:17620408 DOI:10.1083/jcb.200612127]
366 Endoh M,Endo TA,Endoh T,Fujimura Y,Ohara O,Toyoda T,Otte AP,Okano M,Brockdorff N,Vidal M,Koseki H.Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity.Development 2008;135 :1513-1524[PMID:18339675 DOI:10.1242/dev.014340]
367 Aloia L,Di Stefano B,Di Croce L.Polycomb complexes in stem cells and embryonic development.Development 2013;140:2525-2534[PMID:23715546 DOI:10.1242/dev.091553]
368 Ku M,Koche RP,Rheinbay E,Mendenhall EM,Endoh M,Mikkelsen TS,Presser A,Nusbaum C,Xie X,Chi AS,Adli M,Kasif S,Ptaszek LM,Cowan CA,Lander ES,Koseki H,Bernstein BE.Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains.PLo S Genet 2008;4:e1000242[PMID:18974828 DOI:10.1371/journal.pgen.1000242]
369 Schuettengruber B,Chourrout D,Vervoort M,Leblanc B,Cavalli G.Genome regulation by polycomb and trithorax proteins.Cell 2007;128 :735-745[PMID:17320510 DOI:10.1016/j.cell.2007.02.009]
370 Schuettengruber B,Martinez AM,Iovino N,Cavalli G.Trithorax group proteins:switching genes on and keeping them active.Nat Rev Mol Cell Biol 2011;12:799-814[PMID:22108599 DOI:10 .1038/nrm3230]
371 Whetstine JR,Nottke A,Lan F,Huarte M,Smolikov S,Chen Z,Spooner E,Li E,Zhang G,Colaiacovo M,Shi Y.Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases.Cell 2006;125:467-481[PMID:16603238 DOI:10 .1016/j.cell.2006.03.028]
372 Loh YH,Zhang W,Chen X,George J,Ng HH.Jmjd1a and Jmjd2c histone H3 Lys 9 demethylases regulate self-renewal in embryonic stem cells.Genes Dev 2007;21:2545-2557[PMID:17938240DOI:10.1101/gad.1588207]
373 Whyte WA,Bilodeau S,Orlando DA,Hoke HA,Frampton GM,Foster CT,Cowley SM,Young RA.Enhancer decommissioning by LSD1 during embryonic stem cell differentiation.Nature 2012;482:221 -225[PMID:22297846 DOI:10.1038/nature10805]
374 Tachibana M,Sugimoto K,Fukushima T,Shinkai Y.Set domain-containing protein,G9a,is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3.J Biol Chem 2001;276:25309-25317[PMID:11316813 DOI:10.1074/jbc.M101914200]
375 Lee KK,Workman JL.Histone acetyltransferase complexes:one size doesn’t fit all.Nat Rev Mol Cell Biol 2007;8:284-295[PMID:17380162 DOI:10.1038/nrm2145]
376 Wang Z,Zang C,Cui K,Schones DE,Barski A,Peng W,Zhao K.Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes.Cell 2009;138:1019-1031[PMID:19698979 DOI:10.1016/j.cell.2009.06.049]
377 Dovey OM,Foster CT,Cowley SM.Histone deacetylase 1(HDAC1),but not HDAC2,controls embryonic stem cell differentiation.Proc Natl Acad Sci USA 2010;107:8242-8247[PMID:20404188 DOI:10 .1073/pnas.1000478107]
378 Kelly RD,Cowley SM.The physiological roles of histone deacetylase(HDAC)1 and 2:complex co-stars with multiple leading parts.Biochem Soc Trans 2013;41:741-749[PMID:23697933 DOI:10.1042/BST20130010]
379 Kretsovali A,Hadjimichael C,Charmpilas N.Histone deacetylase inhibitors in cell pluripotency,differentiation,and reprogramming.Stem Cells Int 2012;2012:184154[PMID:22550500 DOI:10 .1155/2012/184154]
380 Huangfu D,Maehr R,Guo W,Eijkelenboom A,Snitow M,Chen AE,Melton DA.Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds.Nat Biotechnol 2008;26:795-797[PMID:18568017 DOI:10.1038/nbt1418]
381 Hayakawa T,Nakayama J.Physiological roles of class I HDAC complex and histone demethylase.J Biomed Biotechnol 2011;2011:129383[PMID:21049000 DOI:10.1155/2011/129383]
382 Reynolds N,Latos P,Hynes-Allen A,Loos R,Leaford D,O’Shaughnessy A,Mosaku O,Signolet J,Brennecke P,Kalkan T,Costello I,Humphreys P,Mansfield W,Nakagawa K,Strouboulis J,Behrens A,Bertone P,Hendrich B.NuR D suppresses pluripotency gene expression to promote transcriptional heterogeneity and lineage commitment.Cell Stem Cell 2012;10:583-594[PMID:22560079 DOI:10.1016/j.stem.2012.02.020]
383 Buganim Y,Faddah DA,Cheng AW,Itskovich E,Markoulaki S,Ganz K,Klemm SL,van Oudenaarden A,Jaenisch R.Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase.Cell 2012;150:1209-1222[PMID:22980981 DOI:10.1016/j.cell.2012.08.023]
384 Luo M,Ling T,Xie W,Sun H,Zhou Y,Zhu Q,Shen M,Zong L,Lyu G,Zhao Y,Ye T,Gu J,Tao W,Lu Z,Grummt I.NuR D blocks reprogramming of mouse somatic cells into pluripotent stem cells.Stem Cells 2013;31:1278-1286[PMID:23533168 DOI:10.1002/stem.1374]
385 Yu C,Liu K,Tang S,Ding S.Chemical approaches to cell reprogramming.Curr Opin Genet Dev 2014;28:50-56[PMID:25461450 DOI:10.1016/j.gde.2014.09.006]
386 Fraga MF,Ballestar E,Paz MF,Ropero S,Setien F,Ballestar ML,Heine-Su?er D,Cigudosa JC,Urioste M,Benitez J,Boix-Chornet M,Sanchez-Aguilera A,Ling C,Carlsson E,Poulsen P,Vaag A,Stephan Z,Spector TD,Wu YZ,Plass C,Esteller M.Epigenetic differences arise during the lifetime of monozygotic twins.Proc Natl Acad Sci USA 2005;102:10604-10609[PMID:16009939DOI:10.1073/pnas.0500398102]
387 Seligson DB,Horvath S,Shi T,Yu H,Tze S,Grunstein M,Kurdistani SK.Global histone modification patterns predict risk of prostate cancer recurrence.Nature 2005;435:1262-1266[PMID:15988529 DOI:10.1038/nature03672]
388 Li G,Warden C,Zou Z,Neman J,Krueger JS,Jain A,Jandial R,Chen M.Altered expression of polycomb group genes in glioblastoma multiforme.PLo S One 2013;8:e80970[PMID:24260522 DOI:10.1371/journal.pone.0080970]
389 Valk-Lingbeek ME,Bruggeman SW,van Lohuizen M.Stem cells and cancer;the polycomb connection.Cell 2004;118:409-418[PMID:15315754 DOI:10.1016/j.cell.2004.08.005]
390 Schulte JH,Lim S,Schramm A,Friedrichs N,Koster J,Versteeg R,Ora I,Pajtler K,Klein-Hitpass L,Kuhfittig-Kulle S,Metzger E,Schüle R,Eggert A,Buettner R,Kirfel J.Lysine-specific demethylase 1 is strongly expressed in poorly differentiated neuroblastoma:implications for therapy.Cancer Res 2009;69 :2065-2071[PMID:19223552 DOI:10.1158/0008-5472.CAN-08-1735]
391 Halkidou K,Gaughan L,Cook S,Leung HY,Neal DE,Robson CN.Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer.Prostate 2004;59:177-189[PMID:15042618 DOI:10.1002/pros.20022]
392 Carew JS,Giles FJ,Nawrocki ST.Histone deacetylase inhibitors:mechanisms of cell death and promise in combination cancer therapy.Cancer Lett 2008;269:7-17[PMID:18462867 DOI:10 .1016/j.canlet.2008.03.037]
393 van Vlerken LE,Kiefer CM,Morehouse C,Li Y,Groves C,Wilson SD,Yao Y,Hollingsworth RE,Hurt EM.EZH2 is required for breast and pancreatic cancer stem cell maintenance and can be used as a functional cancer stem cell reporter.Stem Cells Transl Med2013;2:43-52[PMID:23283488 DOI:10.5966/sctm.2012-0036]
394 Iliopoulos D,Hirsch HA,Wang G,Struhl K.Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion.Proc Natl Acad Sci USA 2011;108:1397-1402[PMID:21220315 DOI:10.1073/pnas.1018898108]
395 SuvàML,Riggi N,Janiszewska M,Radovanovic I,Provero P,Stehle JC,Baumer K,Le Bitoux MA,Marino D,Cironi L,Marquez VE,Clément V,Stamenkovic I.EZH2 is essential for glioblastoma cancer stem cell maintenance.Cancer Res 2009;69:9211-9218[PMID:19934320 DOI:10.1158/0008-5472.CAN-09-1622]
396 Crea F,Duhagon MA,Farrar WL,Danesi R.Pharmacogenomics and cancer stem cells:a changing landscape?Trends Pharmacol Sci 2011;32:487-494[PMID:21529973 DOI:10.1016/j.tips.2011.03.010]
397 Richter GH,Plehm S,Fasan A,R?ssler S,Unland R,Bennani-Baiti IM,Hotfilder M,L?wel D,von Luettichau I,Mossbrugger I,Quintanilla-Martinez L,Kovar H,Staege MS,Müller-Tidow C,Burdach S.EZH2 is a mediator of EWS/FLI1 driven tumor growth and metastasis blocking endothelial and neuro-ectodermal differentiation.Proc Natl Acad Sci USA 2009;106:5324-5329[PMID:19289832 DOI:10.1073/pnas.0810759106]
398 Gupta PB,Fillmore CM,Jiang G,Shapira SD,Tao K,Kuperwasser C,Lander ES.Stochastic state transitions give rise to phenotypic equilibrium in populations of cancer cells.Cell 2011;146:633-644[PMID:21854987 DOI:10.1016/j.cell.2011.07.026]
399 Chang B,Li S,He Q,Liu Z,Zhao L,Zhao T,Wang A.Deregulation of Bmi-1 is associated with enhanced migration,invasion and poor prognosis in salivary adenoid cystic carcinoma.Biochim Biophys Acta 2014;1840:3285-3291[PMID:25151043 DOI:10.1016/j.bbagen.2014.08.005]
400 Jin J,Lv X,Chen L,Zhang W,Li J,Wang Q,Wang R,Lu X,Miao D.Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance.Aging Cell2014;13:797-809[PMID:24915841 DOI:10.1111/acel.12236]
401 Yu X,Jiang X,Li H,Guo L,Jiang W,Lu SH.miR-203 inhibits the proliferation and self-renewal of esophageal cancer stem-like cells by suppressing stem renewal factor Bmi-1.Stem Cells Dev 2014;23 :576-585[PMID:24219349 DOI:10.1089/scd.2013.0308]
402 N?r C,Zhang Z,Warner KA,Bernardi L,Visioli F,Helman JI,Roesler R,N?r JE.Cisplatin induces Bmi-1 and enhances the stem cell fraction in head and neck cancer.Neoplasia 2014;16:137-146[PMID:24709421 DOI:10.1593/neo.131744]
403 Liu XF,Yang WT,Xu R,Liu JT,Zheng PS.Cervical cancer cells with positive Sox2 expression exhibit the properties of cancer stem cells.PLoS One 2014;9:e87092[PMID:24489842 DOI:10.1371/journal.pone.0087092]
404 Kreso A,van Galen P,Pedley NM,Lima-Fernandes E,Frelin C,Davis T,Cao L,Baiazitov R,Du W,Sydorenko N,Moon YC,Gibson L,Wang Y,Leung C,Iscove NN,Arrowsmith CH,Szentgyorgyi E,Gallinger S,Dick JE,O’Brien CA.Self-renewal as a therapeutic target in human colorectal cancer.Nat Med 2014;20:29 -36[PMID:24292392 DOI:10.1038/nm.3418]
405 Yu D,Liu Y,Yang J,Jin C,Zhao X,Cheng J,Liu X,Qi X.Clinical implications of BMI-1 in cancer stem cells of laryngeal carcinoma.Cell Biochem Biophys 2015;71:261-269[PMID:25241082 DOI:10 .1007/s12013-014-0194-z]
406 Zhang S,Cui B,Lai H,Liu G,Ghia EM,Widhopf GF,Zhang Z,Wu CC,Chen L,Wu R,Schwab R,Carson DA,Kipps TJ.Ovarian cancer stem cells express ROR1,which can be targeted for anti-cancer-stem-cell therapy.Proc Natl Acad Sci USA 2014;111:17266-17271[PMID:25411317 DOI:10.1073/pnas.1419599111]
407 Iliopoulos D,Lindahl-Allen M,Polytarchou C,Hirsch HA,Tsichlis PN,Struhl K.Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells.Mol Cell 2010;39:761-772[PMID:20832727 DOI:10.1016/j.molcel.2010.08.013]
408 Benoit YD,Witherspoon MS,Laursen KB,Guezguez A,Beauséjour M,Beaulieu JF,Lipkin SM,Gudas LJ.Pharmacological inhibition of polycomb repressive complex-2 activity induces apoptosis in human colon cancer stem cells.Exp Cell Res 2013;319:1463-1470[PMID:23588203 DOI:10.1016/j.yexcr.2013.04.006]
409 Heddleston JM,Wu Q,Rivera M,Minhas S,Lathia JD,Sloan AE,Iliopoulos O,Hjelmeland AB,Rich JN.Hypoxia-induced mixed-lineage leukemia 1 regulates glioma stem cell tumorigenic potential.Cell Death Differ 2012;19:428-439[PMID:21836617 DOI:10 .1038/cdd.2011.109]
410 Wang J,Lu F,Ren Q,Sun H,Xu Z,Lan R,Liu Y,Ward D,Quan J,Ye T,Zhang H.Novel histone demethylase LSD1 inhibitors selectively target cancer cells with pluripotent stem cell properties.Cancer Res 2011;71:7238-7249[PMID:21975933 DOI:10 .1158/0008-5472.CAN-11-0896]
411 Giudice FS,Pinto DS,N?r JE,Squarize CH,Castilho RM.Inhibition of histone deacetylase impacts cancer stem cells and induces epithelial-mesenchyme transition of head and neck cancer.PLo S One 2013;8:e58672[PMID:23527004 DOI:10.1371/journal.pone.0058672]
412 Bernstein E,Kim SY,Carmell MA,Murchison EP,Alcorn H,Li MZ,Mills AA,Elledge SJ,Anderson KV,Hannon GJ.Dicer is essential for mouse development.Nat Genet 2003;35:215-217[PMID:14528307 DOI:10.1038/ng1253]
413 Wang Y,Medvid R,Melton C,Jaenisch R,Blelloch R.DGCR8 is essential for microR NA biogenesis and silencing of embryonic stem cell self-renewal.Nat Genet 2007;39:380-385[PMID:17259983DOI:10.1038/ng1969]
414 Marson A,Levine SS,Cole MF,Frampton GM,Brambrink T,Johnstone S,Guenther MG,Johnston WK,Wernig M,Newman J,Calabrese JM,Dennis LM,Volkert TL,Gupta S,Love J,Hannett N,Sharp PA,Bartel DP,Jaenisch R,Young RA.Connecting microR NA genes to the core transcriptional regulatory circuitry of embryonic stem cells.Cell 2008;134:521-533[PMID:18692474DOI:10.1016/j.cell.2008.07.020]
415 Babiarz JE,Ruby JG,Wang Y,Bartel DP,Blelloch R.Mouse ES cells express endogenous sh RNAs,si RNAs,and other Microprocessor-independent,Dicer-dependent small RNAs.Genes Dev 2008;22:2773-2785[PMID:18923076 DOI:10.1101/gad.1705308]
416 Sinkkonen L,Hugenschmidt T,Berninger P,Gaidatzis D,Mohn F,Artus-Revel CG,Zavolan M,Svoboda P,Filipowicz W.MicroR NAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells.Nat Struct Mol Biol 2008;15:259-267[PMID:18311153 DOI:10 .1038/nsmb.1391]
417 Benetti R,Gonzalo S,Jaco I,Mu?oz P,Gonzalez S,Schoeftner S,Murchison E,Andl T,Chen T,Klatt P,Li E,Serrano M,Millar S,Hannon G,Blasco MA.A mammalian microR NA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases.Nat Struct Mol Biol 2008;15 :268-279[PMID:18311151 DOI:10.1038/nsmb.1399]
418 Wang Y,Xu Z,Jiang J,Xu C,Kang J,Xiao L,Wu M,Xiong J,Guo X,Liu H.Endogenous mi RNA sponge linc RNA-Ro R regulates Oct4,Nanog,and Sox2 in human embryonic stem cell self-renewal.Dev Cell 2013;25:69-80[PMID:23541921 DOI:10 .1016/j.devcel.2013.03.002]
419 Wang Y,Baskerville S,Shenoy A,Babiarz JE,Baehner L,Blelloch R.Embryonic stem cell-specific micro RNAs regulate the G1-S transition and promote rapid proliferation.Nat Genet 2008;40:1478-1483[PMID:18978791 DOI:10.1038/ng.250]
420 Qi J,Yu JY,Shcherbata HR,Mathieu J,Wang AJ,Seal S,Zhou W,Stadler BM,Bourgin D,Wang L,Nelson A,Ware C,Raymond C,Lim LP,Magnus J,Ivanovska I,Diaz R,Ball A,Cleary MA,Ruohola-Baker H.microR NAs regulate human embryonic stem cell division.Cell Cycle 2009;8:3729-3741[PMID:19823043]
421 Sengupta S,Nie J,Wagner RJ,Yang C,Stewart R,Thomson JA.MicroR NA 92b controls the G1/S checkpoint gene p57 in human embryonic stem cells.Stem Cells 2009;27:1524-1528[PMID:19544458 DOI:10.1002/stem.84]
422 Tay YM,Tam WL,Ang YS,Gaughwin PM,Yang H,Wang W,Liu R,George J,Ng HH,Perera RJ,Lufkin T,Rigoutsos I,Thomson AM,Lim B.Micro RNA-134 modulates the differentiation of mouse embryonic stem cells,where it causes post-transcriptional attenuation of Nanog and LRH1.Stem Cells 2008;26:17-29[PMID:17916804 DOI:10.1634/stemcells.2007-0295]
423 Tay Y,Zhang J,Thomson AM,Lim B,Rigoutsos I.MicroR NAs to Nanog,Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation.Nature 2008;455:1124-1128[PMID:18806776DOI:10.1038/nature07299]
424 Xu N,Papagiannakopoulos T,Pan G,Thomson JA,Kosik KS.MicroR NA-145 regulates OCT4,SOX2,and KLF4 and represses pluripotency in human embryonic stem cells.Cell 2009;137:647 -658[PMID:19409607 DOI:10.1016/j.cell.2009.02.038]
425 Singh SK,Kagalwala MN,Parker-Thornburg J,Adams H,Majumder S.REST maintains self-renewal and pluripotency of embryonic stem cells.Nature 2008;453:223-227[PMID:18362916 DOI:10.1038/nature06863]
426 Gangaraju VK,Lin H.MicroR NAs:key regulators of stem cells.Nat Rev Mol Cell Biol 2009;10:116-125[PMID:19165214 DOI:10 .1038/nrm2621]
427 Landgraf P,Rusu M,Sheridan R,Sewer A,Iovino N,Aravin A,Pfeffer S,Rice A,Kamphorst AO,Landthaler M,Lin C,Socci ND,Hermida L,Fulci V,Chiaretti S,FoàR,Schliwka J,Fuchs U,Novosel A,Müller RU,Schermer B,Bissels U,Inman J,Phan Q,Chien M,Weir DB,Choksi R,De Vita G,Frezzetti D,Trompeter HI,Hornung V,Teng G,Hartmann G,Palkovits M,Di Lauro R,Wernet P,Macino G,Rogler CE,Nagle JW,Ju J,Papavasiliou FN,Benzing T,Lichter P,Tam W,Brownstein MJ,Bosio A,Borkhardt A,Russo JJ,Sander C,Zavolan M,Tuschl T.A mammalian microR NA expression atlas based on small RNA library sequencing.Cell 2007;129:1401-1414[PMID:17604727 DOI:10.1016/j.cell.2007.04.040]
428 O’Loghlen A,Mu?oz-Cabello AM,Gaspar-Maia A,Wu HA,Banito A,Kunowska N,Racek T,Pemberton HN,Beolchi P,Lavial F,Masui O,Vermeulen M,Carroll T,Graumann J,Heard E,Dillon N,Azuara V,Snijders AP,Peters G,Bernstein E,Gil J.MicroR NA regulation of Cbx7 mediates a switch of Polycomb orthologs during ESC differentiation.Cell Stem Cell 2012;10:33-46[PMID:22226354 DOI:10.1016/j.stem.2011.12.004]
429 Tarantino C,Paolella G,Cozzuto L,Minopoli G,Pastore L,Parisi S,Russo T.miR NA 34a,100,and 137 modulate differentiation of mouse embryonic stem cells.FASEB J 2010;24:3255-3263[PMID:20439489 DOI:10.1096/fj.09-152207]
430 Melton C,Judson RL,Blelloch R.Opposing microR NA families regulate self-renewal in mouse embryonic stem cells.Nature 2010;463 :621-626[PMID:20054295 DOI:10.1038/nature08725]
431 Viswanathan SR,Daley GQ,Gregory RI.Selective blockade of microR NA processing by Lin28.Science 2008;320:97-100[PMID:18292307 DOI:10.1126/science.1154040]
432 Newman MA,Thomson JM,Hammond SM.Lin-28 interaction with the Let-7 precursor loop mediates regulated micro RNA processing.RNA 2008;14:1539-1549[PMID:18566191 DOI:10 .1261/rna.1155108]
433 Huang TH,Esteller M.Chromatin remodeling in mammary gland differentiation and breast tumorigenesis.Cold Spring Harb Perspect Biol 2010;2:a004515[PMID:20610549 DOI:10.1101/cshperspect.a004515]
434 Yu F,Yao H,Zhu P,Zhang X,Pan Q,Gong C,Huang Y,Hu X,Su F,Lieberman J,Song E.let-7 regulates self renewal and tumorigenicity of breast cancer cells.Cell 2007;131:1109-1123[PMID:18083101 DOI:10.1016/j.cell.2007.10.054]
435 Yu F,Deng H,Yao H,Liu Q,Su F,Song E.Mir-30 reduction maintains self-renewal and inhibits apoptosis in breast tumor-initiating cells.Oncogene 2010;29:4194-4204[PMID:20498642DOI:10.1038/onc.2010.167]
436 Iliopoulos D,Hirsch HA,Struhl K.An epigenetic switch involving NF-kappaB,Lin28,Let-7 MicroR NA,and IL6 links inflammation to cell transformation.Cell 2009;139:693-706[PMID:19878981DOI:10.1016/j.cell.2009.10.014]
437 Shimono Y,Zabala M,Cho RW,Lobo N,Dalerba P,Qian D,Diehn M,Liu H,Panula SP,Chiao E,Dirbas FM,Somlo G,Pera RA,Lao K,Clarke MF.Downregulation of miR NA-200c links breast cancer stem cells with normal stem cells.Cell 2009;138:592-603[PMID:19665978 DOI:10.1016/j.cell.2009.07.011]
438 Gregory PA,Bracken CP,Bert AG,Goodall GJ.Micro RNAs as regulators of epithelial-mesenchymal transition.Cell Cycle 2008;7:3112-3118[PMID:18927505]
439 Park SM,Gaur AB,Lengyel E,Peter ME.The mi R-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.Genes Dev 2008;22:894 -907[PMID:18381893 DOI:10.1101/gad.1640608]
440 Polytarchou C,Iliopoulos D,Struhl K.An integrated trans-criptional regulatory circuit that reinforces the breast cancer stem cell state.Proc Natl Acad Sci USA 2012;109:14470-14475[PMID:22908280 DOI:10.1073/pnas.1212811109]
441 Schraivogel D,Weinmann L,Beier D,Tabatabai G,Eichner A,Zhu JY,Anton M,Sixt M,Weller M,Beier CP,Meister G.CAMTA1 is a novel tumour suppressor regulated by miR-9/9*in glioblastoma stem cells.EMBO J 2011;30:4309-4322[PMID:21857646 DOI:10 .1038/emboj.2011.301]
442 Godlewski J,Nowicki MO,Bronisz A,Williams S,Otsuki A,Nuovo G,Raychaudhury A,Newton HB,Chiocca EA,Lawler S.Targeting of the Bmi-1 oncogene/stem cell renewal factor by microR NA-128inhibits glioma proliferation and self-renewal.Cancer Res 2008;68 :9125-9130[PMID:19010882 DOI:10.1158/0008-5472.CAN-08-2629]
443 Molofsky AV,Pardal R,Iwashita T,Park IK,Clarke MF,Morrison SJ.Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation.Nature 2003;425:962-967[PMID:14574365 DOI:10.1038/nature02060]
444 Li Y,Guessous F,Zhang Y,Dipierro C,Kefas B,Johnson E,Marcinkiewicz L,Jiang J,Yang Y,Schmittgen TD,Lopes B,Schiff D,Purow B,Abounader R.Micro RNA-34a inhibits glioblastoma growth by targeting multiple oncogenes.Cancer Res 2009;69 :7569-7576[PMID:19773441 DOI:10.1158/0008-5472.CAN-09-0529]
445 Yang YP,Chien Y,Chiou GY,Cherng JY,Wang ML,Lo WL,Chang YL,Huang PI,Chen YW,Shih YH,Chen MT,Chiou SH.Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microR NA145 with cationic polyurethane-short branch PEI.Biomaterials 2012;33:1462-1476[PMID:22098779DOI:10.1016/j.biomaterials.2011.10.071]
446 Gal H,Pandi G,Kanner AA,Ram Z,Lithwick-Yanai G,Amariglio N,Rechavi G,Givol D.MIR-451 and Imatinib mesylate inhibit tumor growth of Glioblastoma stem cells.Biochem Biophys Res Commun 2008;376:86-90[PMID:18765229 DOI:10.1016/j.bbrc.2008.08.107]
447 Garzia L,Andolfo I,Cusanelli E,Marino N,Petrosino G,De Martino D,Esposito V,Galeone A,Navas L,Esposito S,Gargiulo S,Fattet S,Donofrio V,Cinalli G,Brunetti A,Vecchio LD,Northcott PA,Delattre O,Taylor MD,Iolascon A,Zollo M.MicroR NA-199b- 5 p impairs cancer stem cells through negative regulation of HES1in medulloblastoma.PLoS One 2009;4:e4998[PMID:19308264DOI:10.1371/journal.pone.0004998]
448 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]
449 Hsieh IS,Chang KC,Tsai YT,Ke JY,Lu PJ,Lee KH,Yeh SD,Hong TM,Chen YL.MicroR NA-320 suppresses the stem cell-like characteristics of prostate cancer cells by downregulating the Wnt/beta-catenin signaling pathway.Carcinogenesis 2013;34:530-538[PMID:23188675 DOI:10.1093/carcin/bgs371]
450 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.MicroR NA mi R-34 inhibits human pancreatic cancer tumor-initiating cells.PLoS One 2009;4:e6816[PMID:19714243 DOI:10.1371/journal.pone.0006816]
451 Ji Q,Hao X,Meng Y,Zhang M,Desano J,Fan D,Xu L.Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres.BMC Cancer 2008;8:266[PMID:18803879 DOI:10.1186/1471-2407-8-266]
452 Bu P,Chen KY,Chen JH,Wang L,Walters J,Shin YJ,Goerger JP,Sun J,Witherspoon M,Rakhilin N,Li J,Yang H,Milsom J,Lee S,Zipfel W,Jin MM,Gümü?ZH,Lipkin SM,Shen X.A microR NA mi R-34a-regulated bimodal switch targets Notch in colon cancer stem cells.Cell Stem Cell 2013;12:602-615[PMID:23642368DOI:10.1016/j.stem.2013.03.002]
453 Sheik Mohamed J,Gaughwin PM,Lim B,Robson P,Lipovich L.Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells.RNA 2010;16:324-337[PMID:20026622 DOI:10.1261/rna.1441510]
454 Chakraborty D,Kappei D,Theis M,Nitzsche A,Ding L,Paszkowski-Rogacz M,Surendranath V,Berger N,Schulz H,Saar K,Hubner N,Buchholz F.Combined RNAi and localization for functionally dissecting long noncoding RNAs.Nat Methods 2012;9:360 -362[PMID:22327834 DOI:10.1038/nmeth.1894]
455 Ng SY,Johnson R,Stanton LW.Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors.EMBO J 2012;31 :522-533[PMID:22193719 DOI:10.1038/emboj.2011.459]
456 Gutschner T,H?mmerle M,Eissmann M,Hsu J,Kim Y,Hung G,Revenko A,Arun G,Stentrup M,Gross M,Z?rnig M,Mac Leod AR,Spector DL,Diederichs S.The noncoding RNA MALAT1is a critical regulator of the metastasis phenotype of lung cancer cells.Cancer Res 2013;73:1180-1189[PMID:23243023 DOI:10 .1158/0008-5472.CAN-12-2850]
457 Guo F,Li Y,Liu Y,Wang J,Li Y,Li G.Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaS ki human cervical cancer cells suppresses cell proliferation and invasion.Acta Biochim Biophys Sin(Shanghai)2010;42:224-229[PMID:20213048]
458 Jiang Y,Li Y,Fang S,Jiang B,Qin C,Xie P,Zhou G,Li G.The role of MALAT1 correlates with HPV in cervical cancer.Oncol Lett2014;7:2135-2141[PMID:24932303 DOI:10.3892/ol.2014.1996]
459 Gupta RA,Shah N,Wang KC,Kim J,Horlings HM,Wong DJ,Tsai MC,Hung T,Argani P,Rinn JL,Wang Y,Brzoska P,Kong B,Li R,West RB,van de Vijver MJ,Sukumar S,Chang HY.Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis.Nature 2010;464:1071-1076[PMID:20393566DOI:10.1038/nature08975]
460 Geng YJ,Xie SL,Li Q,Ma J,Wang GY.Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression.J Int Med Res 2011;39:2119-2128[PMID:22289527]
461 Zhang Y,Xia J,Li Q,Yao Y,Eades G,Gernapudi R,Duru N,Kensler TW,Zhou Q.NRF2/long noncoding RNA ROR signaling regulates mammary stem cell expansion and protects against estrogen genotoxicity.J Biol Chem 2014;289:31310-31318[PMID:25231996 DOI:10.1074/jbc.M114.604868]
462 Marcato P,Dean CA,Giacomantonio CA,Lee PW.Aldehyde dehydrogenase:its role as a cancer stem cell marker comes down to the specific isoform.Cell Cycle 2011;10:1378-1384[PMID:21552008]
463 Miranda-Lorenzo I,Dorado J,Lonardo E,Alcala S,Serrano AG,Clausell-Tormos J,Cioffi M,Megias D,Zagorac S,Balic A,Hidalgo M,Erkan M,Kleeff J,Scarpa A,Sainz B,Heeschen C.Intracellular autofluorescence:a biomarker for epithelial cancer stem cells.Nat Methods 2014;11:1161-1169[PMID:25262208DOI:10.1038/nmeth.3112]
464 Takahashi-Yanaga F,Kahn M.Targeting Wnt signaling:can we safely eradicate cancer stem cells?Clin Cancer Res 2010;16 :3153-3162[PMID:20530697 DOI:10.1158/1078-0432.CCR-09-2943]
465 Justilien V,Fields AP.Molecular pathways:novel approaches for improved therapeutic targeting of Hedgehog signaling in cancer stem cells.Clin Cancer Res 2015;21:505-513[PMID:25646180DOI:10.1158/1078-0432.CCR-14-0507]
466 Kim J,Orkin SH.Embryonic stem cell-specific signatures in cancer:insights into genomic regulatory networks and implications for medicine.Genome Med 2011;3:75[PMID:22126538 DOI:10 .1186/gm291]
467 Rowland BD,Peeper DS.KLF4,p21 and context-dependent opposing forces in cancer.Nat Rev Cancer 2006;6:11-23[PMID:16372018 DOI:10.1038/nrc1780]
468 Yori JL,Seachrist DD,Johnson E,Lozada KL,Abdul-Karim FW,Chodosh LA,Schiemann WP,Keri RA.Krüppel-like factor 4inhibits tumorigenic progression and metastasis in a mouse model of breast cancer.Neoplasia 2011;13:601-610[PMID:21750654]
469 Iv Santaliz-Ruiz LE,Xie X,Old M,Teknos TN,Pan Q.Emerging role of nanog in tumorigenesis and cancer stem cells.Int J Cancer2014;135:2741-2748[PMID:24375318 DOI:10.1002/ijc.28690]
470 SuvàML,Riggi N,Bernstein BE.Epigenetic reprogramming in cancer.Science 2013;339:1567-1570[PMID:23539597 DOI:10 .1126/science.1230184]
471 Mu?oz P,Iliou MS,Esteller M.Epigenetic alterations involved in cancer stem cell reprogramming.Mol Oncol 2012;6:620-636[PMID:23141800 DOI:10.1016/j.molonc.2012.10.006]
472 Kim J,Zaret KS.Reprogramming of human cancer cells to pluripotency for models of cancer progression.EMBO J 2015;34:739 -747[PMID:25712212 DOI:10.15252/embj.201490736]
473 Knoepfler PS.Deconstructing stem cell tumorigenicity:a roadmap to safe regenerative medicine.Stem Cells 2009;27:1050-1056[PMID:19415771 DOI:10.1002/stem.37]
474 Bianco C,Rangel MC,Castro NP,Nagaoka T,Rollman K,Gonzales M,Salomon DS.Role of Cripto-1 in stem cell maintenance and malignant progression.Am J Pathol 2010;177:532-540[PMID:20616345 DOI:10.2353/ajpath.2010.100102]
475 Pacheco-Pinedo EC,Durham AC,Stewart KM,Goss AM,Lu MM,Demayo FJ,Morrisey EE.Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium.J Clin Invest 2011;121:1935-1945[PMID:21490395 DOI:10.1172/JCI44871]
476 Lukacs RU,Memarzadeh S,Wu H,Witte ON.Bmi-1 is a crucial regulator of prostate stem cell self-renewal and malignant transformation.Cell Stem Cell 2010;7:682-693[PMID:21112563DOI:10.1016/j.stem.2010.11.013]
477 di Martino E,Tomlinson DC,Knowles MA.A Decade of FGF Receptor Research in Bladder Cancer:Past,Present,and Future Challenges.Adv Urol 2012;2012:429213[PMID:22899908 DOI:10 .1155/2012/429213]