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http://dx.doi.org/10.5808/GI.2014.12.1.12

Membrane Proteins Involved in Epithelial-Mesenchymal Transition and Tumor Invasion: Studies on TMPRSS4 and TM4SF5  

Kim, Semi (Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology)
Lee, Jung Weon (Department of Pharmacy, College of Pharmacy, Seoul National University)
Publication Information
Genomics & Informatics / v.12, no.1, 2014 , pp. 12-20 More about this Journal
Abstract
The epithelial-mesenchymal transition (EMT) is one mechanism by which cells with mesenchymal features can be generated and is a fundamental event in morphogenesis. Recently, invasion and metastasis of cancer cells from the primary tumor are now thought to be initiated by the developmental process termed the EMT, whereby epithelial cells lose cell polarity and cell-cell interactions, and gain mesenchymal phenotypes with increased migratory and invasive properties. The EMT is believed to be an important step in metastasis and is implicated in cancer progression, although the influence of the EMT in clinical specimens has been debated. This review presents the recent results of two cell surface proteins, the functions and underlying mechanisms of which have recently begun to be demonstrated, as novel regulators of the molecular networks that induce the EMT and cancer progression.
Keywords
epithelial-mesenchymal transition; invasion; membrane proteins; TM4SF5; TMPRSS4;
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1 Rubinstein E. The complexity of tetraspanins. Biochem Soc Trans 2011;39:501-505.   DOI   ScienceOn
2 Lester RD, Jo M, Montel V, Takimoto S, Gonias SL. uPAR induces epithelial-mesenchymal transition in hypoxic breast cancer cells. J Cell Biol 2007;178:425-436.   DOI   ScienceOn
3 Cheng H, Fukushima T, Takahashi N, Tanaka H, Kataoka H. Hepatocyte growth factor activator inhibitor type 1 regulates epithelial to mesenchymal transition through membranebound serine proteinases. Cancer Res 2009;69:1828-1835.   DOI   ScienceOn
4 Li T, Zeng ZC, Wang L, Qiu SJ, Zhou JW, Zhi XT, et al. Radiation enhances long-term metastasis potential of residual hepatocellular carcinoma in nude mice through TMPRSS4-induced epithelial-mesenchymal transition. Cancer Gene Ther 2011;18:617-626.   DOI   ScienceOn
5 Min HJ, Lee Y, Zhao XF, Park YK, Lee MK, Lee JW, et al. TMPRSS4 upregulates uPA gene expression through JNK signaling activation to induce cancer cell invasion. Cell Signal 2014;26:398-408.   DOI   ScienceOn
6 Vleminckx K, Vakaet L Jr, Mareel M, Fiers W, van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 1991;66: 107-119.   DOI   ScienceOn
7 Cavallaro U, Christofori G. Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer 2004;4: 118-132.   DOI   ScienceOn
8 Andreasen D, Vuagniaux G, Fowler-Jaeger N, Hummler E, Rossier BC. Activation of epithelial sodium channels by mouse channel activating proteases (mCAP) expressed in Xenopus oocytes requires catalytic activity of mCAP3 and mCAP2 but not mCAP1. J Am Soc Nephrol 2006;17:968-976.   DOI   ScienceOn
9 Vuagniaux G, Vallet V, Jaeger NF, Hummler E, Rossier BC. Synergistic activation of ENaC by three membrane-bound channel-activating serine proteases (mCAP1, mCAP2, and mCAP3) and serum- and glucocorticoid-regulated kinase (Sgk1) in Xenopus Oocytes. J Gen Physiol 2002;120:191-201.   DOI
10 Jia JB, Wang WQ, Sun HC, Liu L, Zhu XD, Kong LQ, et al. A novel tripeptide, tyroserleutide, inhibits irradiation-induced invasiveness and metastasis of hepatocellular carcinoma in nude mice. Invest New Drugs 2011;29:861-872.   DOI   ScienceOn
11 Cheng D, Kong H, Li Y. Prognostic value of interleukin-8 and MMP-9 in nasopharyngeal carcinoma. Eur Arch Otorhinolaryngol 2014;271:503-509.   DOI   ScienceOn
12 Luo ZY, Wang YY, Zhao ZS, Li B, Chen JF. The expression of TMPRSS4 and Erk1 correlates with metastasis and poor prognosis in Chinese patients with gastric cancer. PLoS One 2013; 8:e70311.   DOI
13 Kim S, Kang HY, Nam EH, Choi MS, Zhao XF, Hong CS, et al. TMPRSS4 induces invasion and epithelial-mesenchymal transition through upregulation of integrin alpha5 and its signaling pathways. Carcinogenesis 2010;31:597-606.   DOI   ScienceOn
14 Nguyen TH, Weber W, Havari E, Connors T, Bagley RG, McLaren R, et al. Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia. Int J Oncol 2012; 41:829-838.   DOI
15 Jung H, Lee KP, Park SJ, Park JH, Jang YS, Choi SY, et al. TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition. Oncogene 2008;27:2635-2647.   DOI   ScienceOn
16 Maschler S, Wirl G, Spring H, Bredow DV, Sordat I, Beug H, et al. Tumor cell invasiveness correlates with changes in integrin expression and localization. Oncogene 2005;24:2032-2041.   DOI   ScienceOn
17 Nam EH, Lee Y, Park YK, Lee JW, Kim S. ZEB2 upregulates integrin alpha5 expression through cooperation with Sp1 to induce invasion during epithelial-mesenchymal transition of human cancer cells. Carcinogenesis 2012;33:563-571.   DOI   ScienceOn
18 Larzabal L, de Aberasturi AL, Redrado M, Rueda P, Rodriguez MJ, Bodegas ME, et al. TMPRSS4 regulates levels of integrin alpha5 in NSCLC through miR-205 activity to promote metastasis. Br J Cancer 2014;110:764-774.   DOI   ScienceOn
19 Bugge TH, Antalis TM, Wu Q. Type II transmembrane serine proteases. J Biol Chem 2009;284:23177-23181.   DOI   ScienceOn
20 Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 2006;25:9-34.   DOI   ScienceOn
21 Duffy MJ. Proteases as prognostic markers in cancer. Clin Cancer Res 1996;2:613-618.
22 Stetler-Stevenson WG, Yu AE. Proteases in invasion: matrix metalloproteinases. Semin Cancer Biol 2001;11:143-152.   DOI   ScienceOn
23 Hooper JD, Clements JA, Quigley JP, Antalis TM. Type II transmembrane serine proteases. Insights into an emerging class of cell surface proteolytic enzymes. J Biol Chem 2001;276: 857-860.   DOI   ScienceOn
24 Netzel-Arnett S, Hooper JD, Szabo R, Madison EL, Quigley JP, Bugge TH, et al. Membrane anchored serine proteases: a rapidly expanding group of cell surface proteolytic enzymes with potential roles in cancer. Cancer Metastasis Rev 2003;22:237-258.   DOI   ScienceOn
25 Szabo R, Bugge TH. Type II transmembrane serine proteases in development and disease. Int J Biochem Cell Biol 2008;40: 1297-1316.   DOI   ScienceOn
26 Ohler A, Becker-Pauly C. TMPRSS4 is a type II transmembrane serine protease involved in cancer and viral infections. Biol Chem 2012;393:907-914.
27 Szabo R, Wu Q, Dickson RB, Netzel-Arnett S, Antalis TM, Bugge TH. Type II transmembrane serine proteases. Thromb Haemost 2003;90:185-193.
28 Kitamoto Y, Yuan X, Wu Q, McCourt DW, Sadler JE. Enterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains. Proc Natl Acad Sci U S A 1994;91:7588-7592.   DOI
29 Adler J, Parmryd I. Quantifying colocalization by correlation: the Pearson correlation coefficient is superior to the Mander's overlap coefficient. Cytometry A 2010;77:733-742.
30 Wallrapp C, Hähnel S, Müller-Pillasch F, Burghardt B, Iwamura T, Ruthenbürger M, et al. A novel transmembrane serine protease (TMPRSS3) overexpressed in pancreatic cancer. Cancer Res 2000;60:2602-2606.
31 Kebebew E, Greenspan FS, Clark OH, Woeber KA, Grunwell J. Extent of disease and practice patterns for medullary thyroid cancer. J Am Coll Surg 2005;200:890-896.   DOI   ScienceOn
32 Kebebew E, Peng M, Reiff E, Treseler P, Woeber KA, Clark OH, et al. A phase II trial of rosiglitazone in patients with thyroglobulin- positive and radioiodine-negative differentiated thyroid cancer. Surgery 2006;140:960-966.   DOI   ScienceOn
33 Fujita N, Sato S, Tsuruo T. Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization. J Biol Chem 2003;278:49254-49260.   DOI
34 Larzabal L, Nguewa PA, Pio R, Blanco D, Sanchez B, Rodríguez MJ, et al. Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology. Br J Cancer 2011;105:1608-1614.   DOI   ScienceOn
35 Cheng D, Kong H, Li Y. TMPRSS4 as a poor prognostic factor for triple-negative breast cancer. Int J Mol Sci 2013;14:14659- 14668.   DOI
36 Kim H, Jung O, Kang M, Lee MS, Jeong D, Ryu J, et al. JNK signaling activity regulates cell-cell adhesions via TM4SF5-mediated p27(Kip1) phosphorylation. Cancer Lett 2012;314: 198-205.   DOI
37 Hidaka T, Hama S, Shrestha P, Saito T, Kajiwara Y, Yamasaki F, et al. The combination of low cytoplasmic and high nuclear expression of p27 predicts a better prognosis in high-grade astrocytoma. Anticancer Res 2009;29:597-603.
38 Chu IM, Hengst L, Slingerland JM. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer 2008;8:253-267.   DOI   ScienceOn
39 Liang J, Zubovitz J, Petrocelli T, Kotchetkov R, Connor MK, Han K, et al. PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat Med 2002;8:1153-1160.   DOI   ScienceOn
40 Besson A, Gurian-West M, Schmidt A, Hall A, Roberts JM. p27Kip1 modulates cell migration through the regulation of RhoA activation. Genes Dev 2004;18:862-876.   DOI   ScienceOn
41 Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 2004;117:927-939.   DOI   ScienceOn
42 Pinto CA, Widodo E, Waltham M, Thompson EW. Breast cancer stem cells and epithelial mesenchymal plasticity: implications for chemoresistance. Cancer Lett 2013;341:56-62.   DOI
43 Bouyssou JM, Manier S, Huynh D, Issa S, Roccaro AM, Ghobrial IM. Regulation of microRNAs in cancer metastasis. Biochim Biophys Acta 2014;1845:255-265.
44 Brabletz S, Brabletz T. The ZEB/miR-200 feedback loop: a motor of cellular plasticity in development and cancer? EMBO Rep 2010;11:670-677.   DOI
45 Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008;133:704-715.   DOI   ScienceOn
46 Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD, et al. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res 2011;9:997-1007.   DOI
47 Bednarz-Knoll N, Alix-Panabieres C, Pantel K. Plasticity of disseminating cancer cells in patients with epithelial malignancies. Cancer Metastasis Rev 2012;31:673-687.   DOI
48 Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM, McAllister F, et al. EMT and dissemination precede pancreatic tumor formation. Cell 2012;148:349-361.   DOI   ScienceOn
49 Yu M, Bardia A, Wittner BS, Stott SL, Smas ME, Ting DT, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 2013;339: 580-584.   DOI
50 Tiwari N, Gheldof A, Tatari M, Christofori G. EMT as the ultimate survival mechanism of cancer cells. Semin Cancer Biol 2012;22:194-207.   DOI
51 Yang J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 2008;14:818-829.   DOI   ScienceOn
52 Kalluri R. EMT: when epithelial cells decide to become mesenchymal- like cells. J Clin Invest 2009;119:1417-1419.   DOI   ScienceOn
53 Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, et al. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 2005; 436:123-127.   DOI   ScienceOn
54 Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009; 139:871-890.   DOI   ScienceOn
55 Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006; 7:131-142.   DOI   ScienceOn
56 Peinado H, Olmeda D, Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 2007;7:415-428.   DOI   ScienceOn
57 Sangiovanni A, Del Ninno E, Fasani P, De Fazio C, Ronchi G, Romeo R, et al. Increased survival of cirrhotic patients with a hepatocellular carcinoma detected during surveillance. Gastroenterology 2004;126:1005-1014.   DOI   ScienceOn
58 Kim JY, Nam JK, Lee SA, Lee MS, Cho SK, Park ZY, et al. Proteasome inhibition causes epithelial-mesenchymal transition upon TM4SF5 expression. J Cell Biochem 2011;112:782-792.   DOI   ScienceOn
59 Kim H, Kang M, Lee SA, Kwak TK, Jung O, Lee HJ, et al. TM4SF5 accelerates G1/S phase progression via cytosolic p27Kip1 expression and RhoA activity. Biochim Biophys Acta 2010;1803:975-982.   DOI   ScienceOn
60 Kang M, Jeong SJ, Park SY, Lee HJ, Kim HJ, Park KH, et al. Antagonistic regulation of transmembrane 4 L6 family member 5 attenuates fibrotic phenotypes in CCl(4)-treated mice. FEBS J 2012;279:625-635.   DOI   ScienceOn
61 Lee SA, Ryu HW, Kim YM, Choi S, Lee MJ, Kwak TK, et al. Blockade of four-transmembrane L6 family member 5 (TM4SF5)-mediated tumorigenicity in hepatocytes by a synthetic chalcone derivative. Hepatology 2009;49:1316-1325.   DOI   ScienceOn
62 Cannito S, Novo E, di Bonzo LV, Busletta C, Colombatto S, Parola M. Epithelial-mesenchymal transition: from molecular mechanisms, redox regulation to implications in human health and disease. Antioxid Redox Signal 2010;12:1383-1430.   DOI   ScienceOn
63 Kang M, Choi S, Jeong SJ, Lee SA, Kwak TK, Kim H, et al. Cross-talk between TGFbeta1 and EGFR signalling pathways induces TM4SF5 expression and epithelial-mesenchymal transition. Biochem J 2012;443:691-700.   DOI   ScienceOn
64 Besson A, Dowdy SF, Roberts JM. CDK inhibitors: cell cycle regulators and beyond. Dev Cell 2008;14:159-169.   DOI   ScienceOn
65 Baldassarre G, Belletti B, Bruni P, Boccia A, Trapasso F, Pentimalli F, et al. Overexpressed cyclin D3 contributes to retaining the growth inhibitor p27 in the cytoplasm of thyroid tumor cells. J Clin Invest 1999;104:865-874.   DOI   ScienceOn
66 Cordon-Cardo C, Koff A, Drobnjak M, Capodieci P, Osman I, Millard SS, et al. Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma. J Natl Cancer Inst 1998;90:1284-1291.   DOI   ScienceOn
67 Lee SA, Kim YM, Kwak TK, Kim HJ, Kim S, Ko W, et al. The extracellular loop 2 of TM4SF5 inhibits integrin alpha2 on hepatocytes under collagen type I environment. Carcinogenesis 2009;30:1872-1879.   DOI   ScienceOn
68 Lee SY, Kim YT, Lee MS, Kim YB, Chung E, Kim S, et al. Focal adhesion and actin organization by a cross-talk of TM4SF5 with integrin alpha2 are regulated by serum treatment. Exp Cell Res 2006;312:2983-2999.   DOI   ScienceOn
69 Choi S, Lee SA, Kwak TK, Kim HJ, Lee MJ, Ye SK, et al. Cooperation between integrin alpha5 and tetraspan TM4SF5 regulates VEGF-mediated angiogenic activity. Blood 2009;113: 1845-1855.   DOI   ScienceOn
70 Lee SA, Lee SY, Cho IH, Oh MA, Kang ES, Kim YB, et al. Tetraspanin TM4SF5 mediates loss of contact inhibition through epithelial-mesenchymal transition in human hepatocarcinoma. J Clin Invest 2008;118:1354-1366.   DOI   ScienceOn
71 Jung O, Choi S, Jang SB, Lee SA, Lim ST, Choi YJ, et al. Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells. J Cell Sci 2012; 125(Pt 24):5960-5973.   DOI   ScienceOn
72 Jung O, Choi YJ, Kwak TK, Kang M, Lee MS, Ryu J, et al. The COOH-terminus of TM4SF5 in hepatoma cell lines regulates c-Src to form invasive protrusions via EGFR Tyr845 phosphorylation. Biochim Biophys Acta 2013;1833:629-642.   DOI   ScienceOn
73 Lee SA, Park KH, Lee JW. Modulation of signaling between TM4SF5 and integrins in tumor microenvironment. Front Biosci (Landmark Ed) 2011;16:1752-1758.   DOI
74 Lee SA, Kim TY, Kwak TK, Kim H, Kim S, Lee HJ, et al. Transmembrane 4 L six family member 5 (TM4SF5) enhances migration and invasion of hepatocytes for effective metastasis. J Cell Biochem 2010;111:59-66.   DOI   ScienceOn
75 Lee MS, Kim HP, Kim TY, Lee JW. Gefitinib resistance of cancer cells correlated with TM4SF5-mediated epithelial-mesenchymal transition. Biochim Biophys Acta 2012;1823:514-523.   DOI   ScienceOn
76 Kaneko R, Tsuji N, Kamagata C, Endoh T, Nakamura M, Kobayashi D, et al. Amount of expression of the tumor- associated antigen L6 gene and transmembrane 4 superfamily member 5 gene in gastric cancers and gastric mucosa. Am J Gastroenterol 2001;96:3457-3458.
77 Wright MD, Ni J, Rudy GB. The L6 membrane proteins: a new four-transmembrane superfamily. Protein Sci 2000;9:1594-1600.   DOI   ScienceOn
78 Gress TM, Wallrapp C, Frohme M, Müller-Pillasch F, Lacher U, Friess H, et al. Identification of genes with specific expression in pancreatic cancer by cDNA representational difference analysis. Genes Chromosomes Cancer 1997;19:97-103.   DOI
79 Müller-Pillasch F, Wallrapp C, Lacher U, Friess H, Büchler M, Adler G, et al. Identification of a new tumour-associated antigen TM4SF5 and its expression in human cancer. Gene 1998; 208:25-30.   DOI   ScienceOn
80 Pascual-Le Tallec L, Dulmet E, Bertagna X, de Keyzer Y. Identification of genes associated with the corticotroph phenotype in bronchial carcinoid tumors. J Clin Endocrinol Metab 2002;87:5015-5022.   DOI
81 Karlsson E, Delle U, Danielsson A, Olsson B, Abel F, Karlsson P, et al. Gene expression variation to predict 10-year survival in lymph-node-negative breast cancer. BMC Cancer 2008;8:254.   DOI   ScienceOn
82 Wu YB, Huang YS, Xu YP, Sun YF, Yu DL, Zhang XQ, et al. A high level of TM4SF5 is associated with human esophageal cancer progression and poor patient survival. Dig Dis Sci 2013;58:2623-2633.   DOI   ScienceOn
83 Andreasen PA, Kjoller L, Christensen L, Duffy MJ. The urokinase- type plasminogen activator system in cancer metastasis: a review. Int J Cancer 1997;72:1-22.   DOI   ScienceOn
84 Hemler ME. Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol 2003;19: 397-422.   DOI   ScienceOn
85 Fuxe J, Vincent T, Garcia de Herreros A. Transcriptional crosstalk between TGF-beta and stem cell pathways in tumor cell invasion: role of EMT promoting Smad complexes. Cell Cycle 2010;9:2363-2374.   DOI
86 Kang S, Min HJ, Kang MS, Jung MG, Kim S. Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors. Bioorg Med Chem Lett 2013;23:1748-1751.   DOI   ScienceOn
87 Jo M, Eastman BM, Webb DL, Stoletov K, Klemke R, Gonias SL. Cell signaling by urokinase-type plasminogen activator receptor induces stem cell-like properties in breast cancer cells. Cancer Res 2010;70:8948-8958.   DOI
88 Sala-Valdes M, Ailane N, Greco C, Rubinstein E, Boucheix C. Targeting tetraspanins in cancer. Expert Opin Ther Targets 2012;16:985-997.   DOI   ScienceOn
89 Detchokul S, Williams ED, Parker MW, Frauman AG. Tetraspanins as regulators of the tumour microenvironment: implications for metastasis and therapeutic strategies. Br J Pharmacol 2013 Jun 3 [Epub]. http://dx.doi.org/10.1111/bph.12260.
90 Yanez-Mo M, Barreiro O, Gordon-Alonso M, Sala-Valdes M, Sánchez-Madrid F. Tetraspanin-enriched microdomains: a functional unit in cell plasma membranes. Trends Cell Biol 2009;19:434-446.   DOI   ScienceOn
91 Berditchevski F. Complexes of tetraspanins with integrins: more than meets the eye. J Cell Sci 2001;114(Pt 23): 4143-4151.
92 Stipp CS, Kolesnikova TV, Hemler ME. Functional domains in tetraspanin proteins. Trends Biochem Sci 2003;28:106-112.   DOI   ScienceOn
93 Berditchevski F, Odintsova E. Tetraspanins as regulators of protein trafficking. Traffic 2007;8:89-96.   DOI   ScienceOn