盘状蛋白结构域受体1与肿瘤细胞信号通路关系的研究进展
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摘要
盘状蛋白结构域受体1(discoidin domain receptor 1,DDR1)是酪氨酸激酶受体(tyrosine kinase receptor,RTK)家族重要成员之一,胶原作为其受体可使其活化,并调节机体多种重要的生理及病理过程,如个体的正常发育、器官纤维化及肿瘤的侵袭和迁移等。最近的多项研究表明DDR1-胶原信号在多种肿瘤中起重要作用。胶原直接通过细胞表面受体与肿瘤细胞相互作用,磷酸化的DDR1对肿瘤细胞的存活及侵袭、迁移等生物学行为起着至关重要的作用。本综述将讨论DDR1在肿瘤细胞增殖、侵袭、细胞粘附中的作用并展望DDR1在肿瘤靶向治疗中的运用前景。
Discoidin domain receptor 1(DDR1) is an important member of the tyrosine kinase receptor(RTK) family. Collagen,as its receptor,can activate and regulate a variety of important physiological and pathological processes,such as individual development,tumor invasion and migration. Recent studies have shown that DDR1-collagen signaling plays vital role in a variety of tumorigenesis. Collagen interacts directly with tumor cells through cell surface receptors,and phosphorylated DDR1 is closely related to survival,invasion,migration and other biological behaviors of tumor cells. This review summarizes the potential role of DDR1 in tumor cell proliferation,invasion,cell adhesion,and the application prospect of DDR1 in cancer targeting therapy.
Discoidin domain receptor 1(DDR1) is an important member of the tyrosine kinase receptor(RTK) family. Collagen,as its receptor,can activate and regulate a variety of important physiological and pathological processes,such as individual development,tumor invasion and migration. Recent studies have shown that DDR1-collagen signaling plays vital role in a variety of tumorigenesis. Collagen interacts directly with tumor cells through cell surface receptors,and phosphorylated DDR1 is closely related to survival,invasion,migration and other biological behaviors of tumor cells. This review summarizes the potential role of DDR1 in tumor cell proliferation,invasion,cell adhesion,and the application prospect of DDR1 in cancer targeting therapy.
引文
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[9] Wu A,Chen Y,Liu Y,et al. miR-199b-5p inhibits triple negative breast cancer cell proliferation,migration and invasion by targeting DDR1[J]. Oncol Lett,2018,16(4):4889-4896.
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[25] Wang Z,Sun X,Bao Y,et al. E2F1 silencing inhibits migration and invasion of osteosarcoma cells via regulating DDR1 expression[J]. Int J Oncol,2017,51(6):1639-1650.
[26] Aguilera KY,Huang H,Du W,et al. Inhibition of discoidin domain receptor 1 reduces collagen-mediated tumorigenicity in pancreatic ductal adenocarcinoma[J]. Mol Cancer Ther,2017,16(11):2473-2485.
[27] Malaguarnera R,Nicolosi ML,Sacco A,et al. Novel cross talk between IGF-IR and DDR1 regulates IGF-IR trafficking,signaling and biological responses[J]. Oncotarget,2015,6(18):16084-16105.
[28] Xiao Q,Jiang Y,Liu Q,et al. Minor typeⅣcollagenα5chain promotes cancer progression through discoidin domain receptor-1[J]. PLoS Genet,2015,11(5):e1005249.
[29] Das S,Ongusaha PP,Yang YS,et al. Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance through nuclear factor-kappaB pathway activation[J]. Cancer Res,2006,66(16):8123-8130.
[30] Kim HG,Hwang SY,Aaronson SA,et al. DDR1 receptor tyrosine kinase promotes prosurvival pathway through Notch1activation[J]. J Biol Chem,2011,286(20):17672-17681.
[31] Shimada K,Nakamura M,Ishida E,et al. Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer[J]. Cancer Sci,2008,99(1):39-45.
[32] Assent D,Bourgot I,Hennuy B,et al. A membrane-type-1matrix metalloproteinase(MT1-MMP)-discoidin domain receptor 1 axis regulates collagen-induced apoptosis in breast cancer cells[J]. PLoS One,2015,10(3):e0116006.
[33] De Craene B,Berx G. Regulatory networks defining EMT during cancer initiation and progression[J]. Nat Rev Cancer,2013,13(2):97-110.
[34] Aokage K,Ishii G,Ohtaki Y,et al. Dynamic molecular changes associated with epithelial-mesenchymal transition and subsequent mesenchymal-epithelial transition in the early phase of metastatic tumor formation[J]. Int J Cancer,2011,128(7):1585-1595.
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[36] Shintani Y,Fukumoto Y,Chaika N,et al. CollagenⅠ-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1[J].J Cell Biol,2008,180(6):1277-1289.
[37] Taube JH,Herschkowitz JI,Komurov K,et al. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes[J]. Proc Natl Acad Sci U S A,2010,107(35):15449-15454.
[38] Koh M,Woo Y,Valiathan RR,et al. Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H-Ras-induced epithelial to mesenchymal transition[J]. Int J Cancer,2015,136(6):E508-E520.
[39] Chung VY,Tan TZ,Huang RL,et al. Loss of discoidin domain receptor 1(DDR1)via CpG methylation during EMT in epithelial ovarian cancer[J]. Gene,2017,635:9-15.
[40] Eswaramoorthy R,Wang CK,Chen WC,et al. DDR1 regulates the stabilization of cell surface E-cadherin and Ecadherin-mediated cell aggregation[J]. J Cell Physiol,2010,224(2):387-397.
[41] Hidalgo-Carcedo C,Hooper S,Chaudhry SI,et al. Collective cell migration requires suppression of actomyosin at cellcell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6[J]. Nat Cell Biol,2011,13(1):49-58.
[42] Wang CZ,Yeh YC,Tang MJ. DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading[J].Am J Physiol Cell Physiol,2009,297(2):C419-C429.
[43] Yeh YC,Wang CZ,Tang MJ. Discoidin domain receptor 1activation suppresses alpha2beta1 integrin-dependent cell spreading through inhibition of Cdc42 activity[J]. J Cell Physiol,2009,218(1):146-156.
[44] Reel B,Korkmaz CG,Arun MZ,et al. The regulation of matrix metalloproteinase expression and the role of discoidin domain receptor 1/2 signalling in zoledronate-treated PC3 cells[J]. J Cancer,2015,6(10):1020-1029.
[45] Castro-Sanchez L,Soto-Guzman A,Guaderrama-Diaz M,et al.Role of DDR1 in the gelatinases secretion induced by native typeⅣcollagen in MDA-MB-231 breast cancer cells[J]. Clin Exp Metastasis,2011,28(5):463-477.
[46] Thiery JP. Epithelial-mesenchymal transitions in tumour progression[J]. Nat Rev Cancer,2002,2(6):442-454.
[47] Valiathan RR,Marco M,Leitinger B,et al. Discoidin domain receptor tyrosine kinases:new players in cancer progression[J]. Cancer Metastasis Rev,2012,31(1-2):295-321.
[48] Jing H,Song J,Zheng J. Discoidin domain receptor 1:new star in cancer-targeted therapy and its complex role in breast carcinoma[J]. Oncol Lett,2018,15(3):3403-3408.
[49] Epanchintsev A,Shyamsunder P,Verma RS,et al. IL-6,IL-8,MMP-2,MMP-9 are overexpressed in Fanconi anemia cells through a NF-κB/TNF-αdependent mechanism[J]. Mol Carcinog,2015,54(12):1686-1699.
[50] Juin A,Di MJ,Leitinger B,et al. Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42-Tuba pathway[J]. J Cell Biol,2014,207(4):517-533.
[51] Yang JC,Zhang Y,He SJ,et al. TM4SF1 promotes metastasis of pancreatic cancer via regulating the expression of DDR1[J]. Sci Rep,2017,7:45895.
[52] Rudra-Ganguly N,Lowe C,Mattie M,et al. Discoidin domain receptor 1 contributes to tumorigenesis through modulation of TGFBI expression[J]. PLoS One,2014,9(11):e111515.
[53] Hu Y,Liu J,Jiang B,et al. MiR-199a-5p loss up-regulated DDR1 aggravated colorectal cancer by activating epithelial-to-mesenchymal transition related signaling[J]. Dig Dis Sci,2014,59(9):2163-2172.
[54] Neuhaus B,Bühren S,B觟ck B,et al. Migration inhibition of mammary epithelial cells by Syk is blocked in the presence of DDR1 receptors[J]. Cell Mol Life Sci,2011,68(22):3757-3770.
[55] Castro-Sanchez L,Soto-Guzman A,Navarro-Tito N,et al. Native typeⅣcollagen induces cell migration through a CD9and DDR1-dependent pathway in MDA-MB-231 breast cancer cells[J]. Eur J Cell Biol,2010,89(11):843-852.
[56] Kadiri M,El AMA,Berrazouane S,et al. Human Th17 Migration in Three-Dimensional Collagen Involves p38MAPK[J]. J Cell Biochem,2017,118(9):2819-2827.
[57] El AMA,Kadiri M,Boisvert M,et al. Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway[J]. Oncotarget,2016,7(29):44975-44990.
[58] Hansen C,Greengard P,Nairn AC,et al. Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDR1[J]. Exp Cell Res,2006,312(20):4011-4018.
[59] Davis MI,Hunt JP,Herrgard S,et al. Comprehensive analysis of kinase inhibitor selectivity[J]. Nat Biotechnol,2011,29(11):1046-1051.
[60] Jeitany M,Leroy C,Tosti P,et al. Inhibition of DDR1-BCR signalling by nilotinib as a new therapeutic strategy for metastatic colorectal cancer[J]. EMBO Mol Med,2018,10(4).
[61] Gao M,Duan L,Luo J,et al. Discovery and optimization of3-(2-(Pyrazolo[1,5-a]pyrimidin-6-yl)ethynyl)benzamides as novel selective and orally bioavailable discoidin domain receptor 1(DDR1)inhibitors[J]. J Med Chem,2013,56(8):3281-3295.
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[64] Hur H,Ham IH,Lee D,et al. Discoidin domain receptor 1activity drives an aggressive phenotype in gastric carcinoma[J]. BMC Cancer,2017,17(1):87.
[65] Kim HG,Tan L,Weisberg EL,et al. Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor[J].ACS Chem Biol,2013,8(10):2145-2150.
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[2] Shrivastava A,Radziejewski C,Campbell E,et al. An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors[J]. Mol Cell,1997,1(1):25-34.
[3] Carafoli F,Mayer MC,Shiraishi K,et al. Structure of the discoidin domain receptor 1 extracellular region bound to an inhibitory Fab fragment reveals features important for signaling[J]. Structure,2012,20(4):688-697.
[4] Carafoli F,Hohenester E. Collagen recognition and transmembrane signalling by discoidin domain receptors[J].Biochim Biophys Acta,2013,1834(10):2187-2194.
[5] Fu HL,Valiathan RR,Arkwright R,et al. Discoidin domain receptors:unique receptor tyrosine kinases in collagen-mediated signaling[J]. J Biol Chem,2013,288(11):7430-7437.
[6] Yeh YC,Wu CC,Wang YK,et al. DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin[J]. Mol Biol Cell,2011,22(7):940-953.
[7] Borza CM,Pozzi A. Discoidin domain receptors in disease[J]. Matrix Biol,2014,34:185-192.
[8] Henriet E,Sala M,Abou HA,et al. Multitasking discoidin domain receptors are involved in several and specific hallmarks of cancer[J]. Cell Adh Migr,2018,12(4):363-377.
[9] Wu A,Chen Y,Liu Y,et al. miR-199b-5p inhibits triple negative breast cancer cell proliferation,migration and invasion by targeting DDR1[J]. Oncol Lett,2018,16(4):4889-4896.
[10] Miao L,Zhu S,Wang Y,et al. Discoidin domain receptor1 is associated with poor prognosis of non-small cell lung cancer and promotes cell invasion via epithelial-to-mesenchymal transition[J]. Med Oncol,2013,30(3):626.
[11] Sirvent A,Lafitte M,Roche S. DDR1 inhibition as a new therapeutic strategy for colorectal cancer[J]. Mol Cell Oncol,2018,5(4):e1465882.
[12] Lee JH,Poudel B,Ki HH,et al. Complement C1q stimulates the progression of hepatocellular tumor through the activation of discoidin domain receptor 1[J]. Sci Rep,2018,8(1):4908.
[13] Deng Y,Zhao F,Hui L,et al. Suppressing miR-199a-3p by promoter methylation contributes to tumor aggressiveness and cisplatin resistance of ovarian cancer through promoting DDR1 expression[J]. J Ovarian Res,2017,10(1):50.
[14] Vella V,Nicolosi ML,Cantafio P,et al. DDR1 regulates thyroid cancer cell differentiation via IGF-2/IR-A autocrine signaling loop[J]. Endocr Relat Cancer,2019,26(1):197-214.
[15] Xie R,Wang X,Qi G,et al. DDR1 enhances invasion and metastasis of gastric cancer via epithelial-mesenchymal transition[J]. Tumour Biol,2016,37(9):12049-12059.
[16] Vogel WF,Abdulhussein R,Ford CE. Sensing extracellular matrix:an update on discoidin domain receptor function[J]. Cell Signal,2006,18(8):1108-1116.
[17] Juskaite V,Corcoran DS,Leitinger B. Collagen induces activation of DDR1 through lateral dimer association and phosphorylation between dimers[J]. Elife,2017,6.
[18] Fu HL,Valiathan RR,Payne L,et al. Glycosylation at Asn211 regulates the activation state of the discoidin domain receptor 1(DDR1)[J]. J Biol Chem,2014,289(13):9275-9287.
[19] Yeh YC,Lin HH,Tang MJ. A tale of two collagen receptors,integrinβ1 and discoidin domain receptor 1,in epithelial cell differentiation[J]. Am J Physiol Cell Physiol,2012,303(12):C1207-C1217.
[20] Lemmon MA,Schlessinger J. Cell signaling by receptor tyrosine kinases[J]. Cell,2010,141(7):1117-1134.
[21] Leitinger B. Discoidin domain receptor functions in physiological and pathological conditions[J]. Int Rev Cell Mol Biol,2014,310:39-87.
[22] Dejmek J,Dib K,J觟nsson M,et al. Wnt-5a and G-protein signaling are required for collagen-induced DDR1 receptor activation and normal mammary cell adhesion[J]. Int J Cancer,2003,103(3):344-351.
[23] Chetoui N,El AMA,Boisvert M,et al. Discoidin domain receptor 1 expression in activated T cells is regulated by the ERK MAP kinase signaling pathway[J]. J Cell Biochem,2011,112(12):3666-3674.
[24] Ongusaha PP,Kim JI,Fang L,et al. p53 induction and activation of DDR1 kinase counteract p53-mediated apoptosis and influence p53 regulation through a positive feedback loop[J]. EMBO J,2003,22(6):1289-1301.
[25] Wang Z,Sun X,Bao Y,et al. E2F1 silencing inhibits migration and invasion of osteosarcoma cells via regulating DDR1 expression[J]. Int J Oncol,2017,51(6):1639-1650.
[26] Aguilera KY,Huang H,Du W,et al. Inhibition of discoidin domain receptor 1 reduces collagen-mediated tumorigenicity in pancreatic ductal adenocarcinoma[J]. Mol Cancer Ther,2017,16(11):2473-2485.
[27] Malaguarnera R,Nicolosi ML,Sacco A,et al. Novel cross talk between IGF-IR and DDR1 regulates IGF-IR trafficking,signaling and biological responses[J]. Oncotarget,2015,6(18):16084-16105.
[28] Xiao Q,Jiang Y,Liu Q,et al. Minor typeⅣcollagenα5chain promotes cancer progression through discoidin domain receptor-1[J]. PLoS Genet,2015,11(5):e1005249.
[29] Das S,Ongusaha PP,Yang YS,et al. Discoidin domain receptor 1 receptor tyrosine kinase induces cyclooxygenase-2 and promotes chemoresistance through nuclear factor-kappaB pathway activation[J]. Cancer Res,2006,66(16):8123-8130.
[30] Kim HG,Hwang SY,Aaronson SA,et al. DDR1 receptor tyrosine kinase promotes prosurvival pathway through Notch1activation[J]. J Biol Chem,2011,286(20):17672-17681.
[31] Shimada K,Nakamura M,Ishida E,et al. Prostate cancer antigen-1 contributes to cell survival and invasion though discoidin receptor 1 in human prostate cancer[J]. Cancer Sci,2008,99(1):39-45.
[32] Assent D,Bourgot I,Hennuy B,et al. A membrane-type-1matrix metalloproteinase(MT1-MMP)-discoidin domain receptor 1 axis regulates collagen-induced apoptosis in breast cancer cells[J]. PLoS One,2015,10(3):e0116006.
[33] De Craene B,Berx G. Regulatory networks defining EMT during cancer initiation and progression[J]. Nat Rev Cancer,2013,13(2):97-110.
[34] Aokage K,Ishii G,Ohtaki Y,et al. Dynamic molecular changes associated with epithelial-mesenchymal transition and subsequent mesenchymal-epithelial transition in the early phase of metastatic tumor formation[J]. Int J Cancer,2011,128(7):1585-1595.
[35] Song J,Chen X,Bai J,et al. Discoidin domain receptor 1(DDR1),a promising biomarker,induces epithelial to mesenchymal transition in renal cancer cells[J]. Tumour Biol,2016,37(8):11509-11521.
[36] Shintani Y,Fukumoto Y,Chaika N,et al. CollagenⅠ-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1[J].J Cell Biol,2008,180(6):1277-1289.
[37] Taube JH,Herschkowitz JI,Komurov K,et al. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes[J]. Proc Natl Acad Sci U S A,2010,107(35):15449-15454.
[38] Koh M,Woo Y,Valiathan RR,et al. Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H-Ras-induced epithelial to mesenchymal transition[J]. Int J Cancer,2015,136(6):E508-E520.
[39] Chung VY,Tan TZ,Huang RL,et al. Loss of discoidin domain receptor 1(DDR1)via CpG methylation during EMT in epithelial ovarian cancer[J]. Gene,2017,635:9-15.
[40] Eswaramoorthy R,Wang CK,Chen WC,et al. DDR1 regulates the stabilization of cell surface E-cadherin and Ecadherin-mediated cell aggregation[J]. J Cell Physiol,2010,224(2):387-397.
[41] Hidalgo-Carcedo C,Hooper S,Chaudhry SI,et al. Collective cell migration requires suppression of actomyosin at cellcell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6[J]. Nat Cell Biol,2011,13(1):49-58.
[42] Wang CZ,Yeh YC,Tang MJ. DDR1/E-cadherin complex regulates the activation of DDR1 and cell spreading[J].Am J Physiol Cell Physiol,2009,297(2):C419-C429.
[43] Yeh YC,Wang CZ,Tang MJ. Discoidin domain receptor 1activation suppresses alpha2beta1 integrin-dependent cell spreading through inhibition of Cdc42 activity[J]. J Cell Physiol,2009,218(1):146-156.
[44] Reel B,Korkmaz CG,Arun MZ,et al. The regulation of matrix metalloproteinase expression and the role of discoidin domain receptor 1/2 signalling in zoledronate-treated PC3 cells[J]. J Cancer,2015,6(10):1020-1029.
[45] Castro-Sanchez L,Soto-Guzman A,Guaderrama-Diaz M,et al.Role of DDR1 in the gelatinases secretion induced by native typeⅣcollagen in MDA-MB-231 breast cancer cells[J]. Clin Exp Metastasis,2011,28(5):463-477.
[46] Thiery JP. Epithelial-mesenchymal transitions in tumour progression[J]. Nat Rev Cancer,2002,2(6):442-454.
[47] Valiathan RR,Marco M,Leitinger B,et al. Discoidin domain receptor tyrosine kinases:new players in cancer progression[J]. Cancer Metastasis Rev,2012,31(1-2):295-321.
[48] Jing H,Song J,Zheng J. Discoidin domain receptor 1:new star in cancer-targeted therapy and its complex role in breast carcinoma[J]. Oncol Lett,2018,15(3):3403-3408.
[49] Epanchintsev A,Shyamsunder P,Verma RS,et al. IL-6,IL-8,MMP-2,MMP-9 are overexpressed in Fanconi anemia cells through a NF-κB/TNF-αdependent mechanism[J]. Mol Carcinog,2015,54(12):1686-1699.
[50] Juin A,Di MJ,Leitinger B,et al. Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42-Tuba pathway[J]. J Cell Biol,2014,207(4):517-533.
[51] Yang JC,Zhang Y,He SJ,et al. TM4SF1 promotes metastasis of pancreatic cancer via regulating the expression of DDR1[J]. Sci Rep,2017,7:45895.
[52] Rudra-Ganguly N,Lowe C,Mattie M,et al. Discoidin domain receptor 1 contributes to tumorigenesis through modulation of TGFBI expression[J]. PLoS One,2014,9(11):e111515.
[53] Hu Y,Liu J,Jiang B,et al. MiR-199a-5p loss up-regulated DDR1 aggravated colorectal cancer by activating epithelial-to-mesenchymal transition related signaling[J]. Dig Dis Sci,2014,59(9):2163-2172.
[54] Neuhaus B,Bühren S,B觟ck B,et al. Migration inhibition of mammary epithelial cells by Syk is blocked in the presence of DDR1 receptors[J]. Cell Mol Life Sci,2011,68(22):3757-3770.
[55] Castro-Sanchez L,Soto-Guzman A,Navarro-Tito N,et al. Native typeⅣcollagen induces cell migration through a CD9and DDR1-dependent pathway in MDA-MB-231 breast cancer cells[J]. Eur J Cell Biol,2010,89(11):843-852.
[56] Kadiri M,El AMA,Berrazouane S,et al. Human Th17 Migration in Three-Dimensional Collagen Involves p38MAPK[J]. J Cell Biochem,2017,118(9):2819-2827.
[57] El AMA,Kadiri M,Boisvert M,et al. Discoidin domain receptor 1 promotes Th17 cell migration by activating the RhoA/ROCK/MAPK/ERK signaling pathway[J]. Oncotarget,2016,7(29):44975-44990.
[58] Hansen C,Greengard P,Nairn AC,et al. Phosphorylation of DARPP-32 regulates breast cancer cell migration downstream of the receptor tyrosine kinase DDR1[J]. Exp Cell Res,2006,312(20):4011-4018.
[59] Davis MI,Hunt JP,Herrgard S,et al. Comprehensive analysis of kinase inhibitor selectivity[J]. Nat Biotechnol,2011,29(11):1046-1051.
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