Functions of EpCAM in physiological processes and diseases (Review)

Herlyn M, Steplewski Z, Herlyn D and Koprowski H: Colorectal carcinoma-specific antigen: Detection by means of monoclonal antibodies. Proc Natl Acad Sci USA. 76:1438–1442. 1979. View Article : Google Scholar : PubMed/NCBI

Schnell U, Cirulli V and Giepmans BN: EpCAM: Structure and function in health and disease. Biochim Biophys Acta. 1828:1989–2001. 2013. View Article : Google Scholar : PubMed/NCBI

Balzar M, Winter MJ, De Boer CJ and Litvinov SV: The biology of the 17-1A antigen (Ep-C AM). J Mol Med (Berl). 77:699–712. 1999. View Article : Google Scholar

Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao HL, Moss N, Melhem A, McClelland R, Turner W, et al: Human hepatic stem cells from fetal and postnatal donors. J Exp Med. 204:1973–1987. 2007. View Article : Google Scholar : PubMed/NCBI

Kamimoto K, Kaneko K, Kok CY, Okada H, Miyajima A and Itoh T: Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling. Elife. 5:e150342016. View Article : Google Scholar : PubMed/NCBI

Sivagnanam M, Mueller JL, Lee H, Chen Z, Nelson SF, Turner D, Zlotkin SH, Pencharz PB, Ngan BY, Libiger O, et al: Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology. 135:429–437. 2008. View Article : Google Scholar : PubMed/NCBI

Lei Z, Maeda T, Tamura A, Nakamura T, Yamazaki Y, Shiratori H, Yashiro K, Tsukita S and Hamada H: EpCAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins. Dev Biol. 371:136–145. 2012. View Article : Google Scholar : PubMed/NCBI

Guerra E, Lattanzio R, La Sorda R, Dini F, Tiboni GM, Piantelli M and Alberti S: mTrop1/Epcam knockout mice develop congenital tufting enteropathy through dysregulation of intestinal E-cadherin/β-catenin. PLos One. 7:e493022012. View Article : Google Scholar

Mueller JL, McGeough MD, Peña CA and Sivagnanam M: Functional consequences of EpCam mutation in mice and men. Am J Physiol Gastrointest Liver Physiol. 306:G278–G288. 2014. View Article : Google Scholar :

Nagao K, Zhu J, Heneghan MB, Hanson JC, Morasso MI, Tessarollo L, Mackem S and Udey MC: Abnormal placental development and early embryonic lethality in EpCAM-null mice. PLos One. 4:e85432009. View Article : Google Scholar :

Gaiser MR, Lämmermann T, Feng X, Igyarto BZ, Kaplan DH, Tessarollo L, Germain RN and Udey MC: Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo. Proc Natl Acad Sci USA. 109:E889–E897. 2012. View Article : Google Scholar : PubMed/NCBI

Slanchev K, Carney TJ, Stemmler MP, Koschorz B, Amsterdam A, Schwarz H and Hammerschmidt M: The epithelial cell adhesion molecule EpCAM is required for epithelial morphogenesis and integrity during zebrafish epiboly and skin development. PLos Genet. 5:e10005632009. View Article : Google Scholar : PubMed/NCBI

Maghzal N, Vogt E, Reintsch W, Fraser JS and Fagotto F: The tumor-associated EpCAM regulates morphogenetic movements through intracellular signaling. J Cell Biol. 191:645–659. 2010. View Article : Google Scholar : PubMed/NCBI

Maghzal N, Kayali HA, Rohani N, Kajava AV and Fagotto F: EpCAM controls actomyosin contractility and cell adhesion by direct inhibition of PKC. Dev Cell. 27:263–277. 2013. View Article : Google Scholar : PubMed/NCBI

Lu H, Ma J, Yang Y, Shi W and Luo L: EpCAM is an endoderm-specific Wnt derepressor that licenses hepatic development. Dev Cell. 24:543–553. 2013. View Article : Google Scholar : PubMed/NCBI

Trzpis M, McLaughlin PM, De Leij LM and Harmsen MC: Epithelial cell adhesion molecule: More than a carcinoma marker and adhesion molecule. Am J Pathol. 171:386–395. 2007. View Article : Google Scholar : PubMed/NCBI

Cirulli V, Crisa L, Beattie GM, Mally MI, Lopez AD, Fannon A, Ptasznik A, Inverardi L, Ricordi C, Deerinck T, et al: KSA antigen Ep-CAM mediates cell-cell adhesion of pancreatic epithelial cells: Morphoregulatory roles in pancreatic islet development. J Cell Biol. 140:1519–1534. 1998. View Article : Google Scholar : PubMed/NCBI

Lipinski M, Parks DR, Rouse RV and Herzenberg LA: Human trophoblast cell-surface antigens defined by monoclonal antibodies. Proc Natl Acad Sci USA. 78:5147–5150. 1981. View Article : Google Scholar : PubMed/NCBI

Sherwood RI, Jitianu C, Cleaver O, Shaywitz DA, Lamenzo JO, Chen AE, Golub TR and Melton DA: Prospective isolation and global gene expression analysis of definitive and visceral endoderm. Dev Biol. 304:541–555. 2007. View Article : Google Scholar : PubMed/NCBI

Poon CE, Madawala RJ, Day ML and Murphy CR: EpCAM is decreased but is still present in uterine epithelial cells during early pregnancy in the rat: Potential mechanism for maintenance of mucosal integrity during implantation. Cell Tissue Res. 359:655–664. 2015. View Article : Google Scholar

Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, et al: Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 104:10158–10163. 2007. View Article : Google Scholar : PubMed/NCBI

Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, Jia H, Ye Q, Qin LX, Wauthier E, et al: EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 136:1012–1024. 2009. View Article : Google Scholar : PubMed/NCBI

Baeuerle PA and Gires O: EpCAM (CD326) finding its role in cancer. Br J Cancer. 96:417–423. 2007. View Article : Google Scholar : PubMed/NCBI

Ladwein M, Pape UF, Schmidt DS, Schnölzer M, Fiedler S, Langbein L, Franke WW, Moldenhauer G and Zöller M: The cell-cell adhesion molecule EpCAM interacts directly with the tight junction protein claudin-7. Exp Cell Res. 309:345–357. 2005. View Article : Google Scholar : PubMed/NCBI

Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, Kieu C, Papior P, Baeuerle PA, Munz M and Gires O: Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol. 11:162–171. 2009. View Article : Google Scholar : PubMed/NCBI

Dollé L, Theise ND, Schmelzer E, Boulter L, Gires O and van Grunsven LA: EpCAM and the biology of hepatic stem/progenitor cells. Am J Physiol Gastrointest Liver Physiol. 308:G233–G250. 2015. View Article : Google Scholar :

Litvinov SV, Velders MP, Bakker HA, Fleuren GJ and Warnaar SO: Ep-CAM: A human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol. 125:437–446. 1994. View Article : Google Scholar : PubMed/NCBI

Zhang C, Liu LW, Sun WJ, Qin SH, Qin LZ and Wang X: Expressions of E-cadherin, p120ctn, β-catenin and NF-κB in ulcerative colitis. J Huazhong Univ Sci Technolog Med Sci. 35:368–373. 2015. View Article : Google Scholar : PubMed/NCBI

Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Löchner D and Birchmeier W: E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 113:173–185. 1991. View Article : Google Scholar : PubMed/NCBI

Berx G, Nollet F and van Roy F: Dysregulation of the E-cadherin/catenin complex by irreversible mutations in human carcinomas. Cell Adhes Commun. 6:171–184. 1998. View Article : Google Scholar : PubMed/NCBI

Handschuh G, Candidus S, Luber B, Reich U, Schott C, Oswald S, Becke H, Hutzler P, Birchmeier W, Höfler H and Becker KF: Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility. Oncogene. 18:4301–4312. 1999. View Article : Google Scholar : PubMed/NCBI

Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A and Reeve AE: E-cadherin germline mutations in familial gastric cancer. Nature. 392:402–405. 1998. View Article : Google Scholar : PubMed/NCBI

Gayther SA, Gorringe KL, Ramus SJ, Huntsman D, Roviello F, Grehan N, Machado JC, Pinto E, Seruca R, Halling K, et al: Identification of germ-line E-cadherin mutations in gastric cancer families of European origin. Cancer Res. 58:4086–4089. 1998.PubMed/NCBI

Corso G, Marrelli D and Roviello F: Familial gastric cancer and germline mutations of E-cadherin. Ann Ital Chir. 83:177–182. 2012.PubMed/NCBI

Litvinov SV, Balzar M, Winter MJ, Bakker HA, Briaire-De Bruijn IH, Prins F, Fleuren GJ and Warnaar SO: Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins. J Cell Biol. 139:1337–1348. 1997. View Article : Google Scholar

Winter MJ, Nagelkerken B, Mertens AE, Rees-Bakker HA, Briaire-De Bruijn IH and Litvinov SV: Expression of Ep-CAM shifts the state of cadherin-mediated adhesions from strong to weak. Exp Cell Res. 285:50–58. 2003. View Article : Google Scholar : PubMed/NCBI

Kozan PA, McGeough MD, Peña CA, Mueller JL, Barrett KE, Marchelletta RR and Sivagnanam M: Mutation of EpCAM leads to intestinal barrier and ion transport dysfunction. J Mol Med (Berl). 93:535–545. 2015. View Article : Google Scholar

Bondow BJ, Faber ML, Wojta KJ, Walker EM and Battle MA: E-cadherin is required for intestinal morphogenesis in the mouse. Dev Biol. 371:1–12. 2012. View Article : Google Scholar : PubMed/NCBI

Tunggal JA, Helfrich I, Schmitz A, Schwarz H, Günzel D, Fromm M, Kemler R, Krieg T and Niessen CM: E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO J. 24:1146–1156. 2005. View Article : Google Scholar : PubMed/NCBI

Patey N, Scoazec JY, Cuenod-Jabri B, Canioni D, Kedinger M, Goulet O and Brousse N: Distribution of cell adhesion molecules in infants with intestinal epithelial dysplasia (tufting enteropathy). Gastroenterology. 113:833–843. 1997. View Article : Google Scholar : PubMed/NCBI

Wu CJ, Mannan P, Lu M and Udey MC: Epithelial cell adhesion molecule (EpCAM) regulates claudin dynamics and tight junctions. J Biol Chem. 288:12253–12268. 2013. View Article : Google Scholar : PubMed/NCBI

Salomon J, Gaston C, Magescas J, Duvauchelle B, Canioni D, Sengmanivong L, Mayeux A, Michaux G, Campeotto F, Lemale J, et al: Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity. Nat Commun. 8:139982017. View Article : Google Scholar : PubMed/NCBI

Kuhn S, Koch M, Nübel T, Ladwein M, Antolovic D, Klingbeil P, Hildebrand D, Moldenhauer G, Langbein L, Franke WW, et al: A complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression. Mol Cancer Res. 5:553–567. 2007. View Article : Google Scholar : PubMed/NCBI

Nübel T, Preobraschenski J, Tuncay H, Weiss T, Kuhn S, Ladwein M, Langbein L and Zöller M: Claudin-7 regulates EpCAM-mediated functions in tumor progression. Mol Cancer Res. 7:285–299. 2009. View Article : Google Scholar : PubMed/NCBI

Fujita H, Chiba H, Yokozaki H, Sakai N, Sugimoto K, Wada T, Kojima T, Yamashita T and Sawada N: Differential expression and subcellular localization of claudin-7, -8, -12, -13, and -15 along the mouse intestine. J Histochem Cytochem. 54:933–944. 2006. View Article : Google Scholar : PubMed/NCBI

Hewitt KJ, Agarwal R and Morin PJ: The claudin gene family: Expression in normal and neoplastic tissues. BMC Cancer. 6:1862006. View Article : Google Scholar : PubMed/NCBI

Ding L, Lu Z, Foreman O, Tatum R, Lu Q, Renegar R, Cao J and Chen YH: Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice. Gastroenterology. 142:305–315. 2012. View Article : Google Scholar :

Nakatsukasa M, Kawasaki S, Yamasaki K, Fukuoka H, Matsuda A, Tsujikawa M, Tanioka H, Nagata-Takaoka M, Hamuro J and Kinoshita S: Tumor-associated calcium signal transducer 2 is required for the proper subcellular localization of claudin 1 and 7: Implications in the pathogenesis of gelatinous drop-like corneal dystrophy. Am J Pathol. 177:1344–1355. 2010. View Article : Google Scholar : PubMed/NCBI

Daugherty BL, Ward C, Smith T, Ritzenthaler JD and Koval M: Regulation of heterotypic claudin compatibility. J Biol Chem. 282:30005–30013. 2007. View Article : Google Scholar : PubMed/NCBI

Furuse M, Sasaki H and Tsukita S: Manner of interaction of heterogeneous claudin species within and between tight junction strands. J Cell Biol. 147:891–903. 1999. View Article : Google Scholar : PubMed/NCBI

Piontek J, Winkler L, Wolburg H, Müller SL, Zuleger N, Piehl C, Wiesner B, Krause G and Blasig IE: Formation of tight junction: Determinants of homophilic interaction between classic claudins. FASEB J. 22:146–158. 2008. View Article : Google Scholar

Tatum R, Zhang Y, Salleng K, Lu Z, Lin JJ, Lu Q, Jeansonne BG, Ding L and Chen YH: Renal salt wasting and chronic dehydration in claudin-7-deficient mice. Am J Physiol Renal Physiol. 298:F24–F34. 2010. View Article : Google Scholar :

Gladden AB, Hebert AM, Schneeberger EE and McClatchey AI: The NF2 tumor suppressor, Merlin, regulates epidermal development through the establishment of a junctional polarity complex. Dev Cell. 19:727–739. 2010. View Article : Google Scholar : PubMed/NCBI

Tinkle CL, Pasolli HA, Stokes N and Fuchs E: New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity. Proc Natl Acad Sci USA. 105:15405–15410. 2008. View Article : Google Scholar : PubMed/NCBI

Vasioukhin V, Bauer C, Degenstein L, Wise B and Fuchs E: Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell. 104:605–617. 2001. View Article : Google Scholar : PubMed/NCBI

Shin K, Fogg VC and Margolis B: Tight junctions and cell polarity. Annu Rev Cell Dev Biol. 22:207–235. 2006. View Article : Google Scholar : PubMed/NCBI

Tepass U: Claudin complexities at the apical junctional complex. Nat Cell Biol. 5:595–597. 2003. View Article : Google Scholar : PubMed/NCBI

Van Campenhout CA, Eitelhuber A, Gloeckner CJ, Giallonardo P, Gegg M, Oller H, Grant SG, Krappmann D, Ueffing M and Lickert H: Dlg3 trafficking and apical tight junction formation is regulated by nedd4 and nedd4-2 e3 ubiquitin ligases. Dev Cell. 21:479–491. 2011. View Article : Google Scholar : PubMed/NCBI

Goulet O, Kedinger M, Brousse N, Cuenod B, Colomb V, Patey N, De Potter S, Mougenot JF, Canioni D, Cerf-Bensussan N, et al: Intractable diarrhea of infancy with epithelial and basement membrane abnormalities. J Pediatr. 127:212–219. 1995. View Article : Google Scholar : PubMed/NCBI

Goulet O, Salomon J, Ruemmele F, De Serres NP and Brousse N: Intestinal epithelial dysplasia (tufting enteropathy). Orphanet J Rare Dis. 2:202007. View Article : Google Scholar : PubMed/NCBI

Beaulieu JF: Differential expression of the VLA family of integrins along the crypt-villus axis in the human small intestine. J Cell Sci. 102:427–436. 1992.PubMed/NCBI

Simon-Assmann P, Bouziges F, Vigny M and Kedinger M: Origin and deposition of basement membrane heparan sulfate proteoglycan in the developing intestine. J Cell Biol. 109:1837–1848. 1989. View Article : Google Scholar : PubMed/NCBI

Simon-Assmann P, Duclos B, Orian-Rousseau V, Arnold C, Mathelin C, Engvall E and Kedinger M: Differential expression of laminin isoforms and alpha 6-beta 4 integrin subunits in the developing human and mouse intestine. Dev Dyn. 201:71–85. 1994. View Article : Google Scholar : PubMed/NCBI

Simon-Assmann P and Kedinger M: Heterotypic cellular cooperation in gut morphogenesis and differentiation. Semin Cell Biol. 4:221–230. 1993. View Article : Google Scholar : PubMed/NCBI

Simo P, Simon-Assmann P, Bouziges F, Leberquier C, Kedinger M, Ekblom P and Sorokin L: Changes in the expression of laminin during intestinal development. Development. 112:477–487. 1991.PubMed/NCBI

Simo P, Bouziges F, Lissitzky JC, Sorokin L, Kedinger M and Simon-Assmann P: Dual and asynchronous deposition of laminin chains at the epithelial-mesenchymal interface in the gut. Gastroenterology. 102:1835–1845. 1992. View Article : Google Scholar : PubMed/NCBI

Tamura A, Hayashi H, Imasato M, Yamazaki Y, Hagiwara A, Wada M, Noda T, Watanabe M, Suzuki Y and Tsukita S: Loss of claudin-15, but not claudin-2, causes Na⁺ deficiency and glucose malabsorption in mouse small intestine. Gastroenterology. 140:913–923. 2011. View Article : Google Scholar

Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, et al: Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 4:270662015. View Article : Google Scholar : PubMed/NCBI

Colombo M, Raposo G and Théry C: Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 30:255–289. 2014. View Article : Google Scholar : PubMed/NCBI

Tkach M and Théry C: Communication by extracellular vesicles: Where we are and where we need to go. Cell. 164:1226–1232. 2016. View Article : Google Scholar : PubMed/NCBI

Iwai S, Kurosu S, Sasaki H, Kato K and Maekawa T: Trapping and proliferation of target cells on C60 fullerene nano fibres. Heliyon. 3:e003862017. View Article : Google Scholar :

Jiang L, Shen Y, Guo D, Yang D, Liu J, Fei X, Yang Y, Zhang B, Lin Z, Yang F, et al: Corrigendum: EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance. Nat Commun. 8:160062017. View Article : Google Scholar : PubMed/NCBI

Cai Z, Zhang W, Yang F, Yu L, Yu Z, Pan J, Wang L, Cao X and Wang J: Immunosuppressive exosomes from TGF-β1 gene-modified dendritic cells attenuate Th17-mediated inflammatory autoimmune disease by inducing regulatory T cells. Cell Res. 22:607–610. 2012. View Article : Google Scholar

Yu L, Yang F, Jiang L, Chen Y, Wang K, Xu F, Wei Y, Cao X, Wang J and Cai Z: Exosomes with membrane-associated TGF-β1 from gene-modified dendritic cells inhibit murine EAE independently of MHC restriction. Eur J Immunol. 43:2461–2472. 2013. View Article : Google Scholar : PubMed/NCBI

Villablanca EJ, Renucci A, Sapède D, Lec V, Soubiran F, Sandoval PC, Dambly-Chaudière C, Ghysen A and Allende ML: Control of cell migration in the zebrafish lateral line: Implication of the gene 'tumour-associated calcium signal transducer,' tacstd. Dev Dyn. 235:1578–1588. 2006. View Article : Google Scholar : PubMed/NCBI

Aman A and Piotrowski T: Wnt/beta-catenin and Fgf signaling control collective cell migration by restricting chemokine receptor expression. Dev Cell. 15:749–761. 2008. View Article : Google Scholar : PubMed/NCBI

Sarrach S, Huang Y, Niedermeyer S, Hachmeister M, Fischer L, Gille S, Pan M, Mack B, Kranz G, Libl D, et al: Spatiotemporal patterning of EpCAM is important for murine embryonic endo- and mesodermal differentiation. Sci Rep. 8:18012018. View Article : Google Scholar : PubMed/NCBI

De Boer CJ, Van Krieken JH, Janssen-Van Rhijn CM and Litvinov SV: Expression of Ep-CAM in normal, regenerating, metaplastic, and neoplastic liver. J Pathol. 188:201–206. 1999. View Article : Google Scholar : PubMed/NCBI

Münz M, Kieu C, Mack B, Schmitt B, Zeidler R and Gires O: The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 23:5748–5758. 2004. View Article : Google Scholar : PubMed/NCBI

Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, Cole DJ and Gillanders WE: EpCAM is over expressed in breast cancer and is a potential target for breast cancer gene therapy. Cancer Res. 64:5818–5824. 2004. View Article : Google Scholar : PubMed/NCBI

Schmelzer E, Wauthier E and Reid LM: The phenotypes of pluripotent human hepatic progenitors. Stem Cells. 24:1852–1858. 2006. View Article : Google Scholar : PubMed/NCBI

Zhang L, Theise N, Chua M and Reid LM: The stem cell niche of human livers: Symmetry between development and regeneration. Hepatology. 48:1598–1607. 2008. View Article : Google Scholar : PubMed/NCBI

Shimazaki T, Okazawa H, Fujii H, Ikeda M, Tamai K, McKay RD, Muramatsu M and Hamada H: Hybrid cell extinction and re-expression of Oct-3 function correlates with differentiation potential. EMBO J. 12:4489–4498. 1993.PubMed/NCBI

González B, Denzel S, Mack B, Conrad M and Gires O: EpCAM is involved in maintenance of the murine embryonic stem cell phenotype. Stem Cells. 27:1782–1791. 2009. View Article : Google Scholar : PubMed/NCBI

Lu TY, Lu RM, Liao MY, Yu J, Chung CH, Kao CF and Wu HC: Epithelial cell adhesion molecule regulation is associated with the maintenance of the undifferentiated phenotype of human embryonic stem cells. J Biol Chem. 285:8719–8732. 2010. View Article : Google Scholar : PubMed/NCBI

Okabe M, Tsukahara Y, Tanaka M, Suzuki K, Saito S, Kamiya Y, Tsujimura T, Nakamura K and Miyajima A: Potential hepatic stem cells reside in EpCAM⁺ cells of normal and injured mouse liver. Development. 136:1951–1960. 2009. View Article : Google Scholar : PubMed/NCBI

Tanaka M, Okabe M, Suzuki K, Kamiya Y, Tsukahara Y, Saito S and Miyajima A: Mouse hepatoblasts at distinct developmental stages are characterized by expression of EpCAM and DLK1: Drastic change of EpCAM expression during liver development. Mech Dev. 126:665–676. 2009. View Article : Google Scholar : PubMed/NCBI

Hachmeister M, Bobowski KD, Hogl S, Dislich B, Fukumori A, Eggert C, Mack B, Kremling H, Sarrach S, Coscia F, et al: Regulated intramembrane proteolysis and degradation of murine epithelial cell adhesion molecule mEpCAM. PLos One. 8:e718362013. View Article : Google Scholar : PubMed/NCBI

Huang HP, Chen PH, Yu CY, Chuang CY, Stone L, Hsiao WC, Li CL, Tsai SC, Chen KY, Chen HF, et al: Epithelial cell adhesion molecule (EpCAM) complex proteins promote transcription factor-mediated pluripotency reprogramming. J Biol Chem. 286:33520–33532. 2011. View Article : Google Scholar : PubMed/NCBI

Yu T, Ma Y and Wang H: EpCAM intracellular domain promotes porcine cell reprogramming by upregulation of pluripotent gene expression via beta-catenin signaling. Sci Rep. 7:463152017. View Article : Google Scholar : PubMed/NCBI

Kuan II, Liang KH, Wang YP, Kuo TW, Meir YJ, Wu SC, Yang SC, Lu J and Wu HC: EpEX/EpCAM and Oct4 or Klf4 alone are sufficient to generate induced pluripotent stem cells through STAT3 and HIF2α. Sci Rep. 7:418522017. View Article : Google Scholar

Salomon J, Goulet O, Canioni D, Brousse N, Lemale J, Tounian P, Coulomb A, Marinier E, Hugot JP, Ruemmele F, et al: Genetic characterization of congenital tufting enteropathy: Epcam associated phenotype and involvement of SPINT2 in the syndromic form. Hum Genet. 133:299–310. 2014. View Article : Google Scholar

Slae MA, Saginur M, Persad R, Yap J, Lacson A, Salomon J, Canioni D and Huynh HQ: Syndromic congenital diarrhea because of the SPINT2 mutation showing enterocyte tufting and unique electron microscopy findings. Clin Dysmorphol. 22:118–120. 2013. View Article : Google Scholar : PubMed/NCBI

Furuse M, Furuse K, Sasaki H and Tsukita S: Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells. J Cell Biol. 153:263–272. 2001. View Article : Google Scholar : PubMed/NCBI

Van Itallie CM, Fanning AS and Anderson JM: Reversal of charge selectivity in cation or anion-selective epithelial lines by expression of different claudins. Am J Physiol Renal Physiol. 285:F1078–F1084. 2003. View Article : Google Scholar : PubMed/NCBI

Hou J, Gomes AS, Paul DL and Goodenough DA: Study of claudin function by RNA interference. J Biol Chem. 281:36117–36123. 2006. View Article : Google Scholar : PubMed/NCBI

Amasheh S, Meiri N, Gitter AH, Schöneberg T, Mankertz J, Schulzke JD and Fromm M: Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci. 115:4969–4976. 2002. View Article : Google Scholar : PubMed/NCBI

Yu AS, Cheng MH, Angelow S, Günzel D, Kanzawa SA, Schneeberger EE, Fromm M and Coalson RD: Molecular basis for cation selectivity in claudin-2-based paracellular pores: Identification of an electrostatic interaction site. J Gen Physiol. 133:111–127. 2009. View Article : Google Scholar :

Schultz SG and Curran PF: Coupled transport of sodium and organic solutes. Physiol Rev. 50:637–718. 1970. View Article : Google Scholar : PubMed/NCBI

Kapus A and Szászi K: Coupling between apical and paracellular transport processes. Biochem Cell Biol. 84:870–880. 2006. View Article : Google Scholar

Tsukaguchi H, Tokui T, Mackenzie B, Berger UV, Chen XZ, Wang Y, Brubaker RF and Hediger MA: A family of mammalian Na⁺-dependent L-ascorbic acid transporters. Nature. 399:70–75. 1999. View Article : Google Scholar : PubMed/NCBI

Holmes JL, Van Itallie CM, Rasmussen JE and Anderson JM: Claudin profiling in the mouse during postnatal intestinal development and along the gastrointestinal tract reveals complex expression patterns. Gene Expr Patterns. 6:581–588. 2006. View Article : Google Scholar : PubMed/NCBI

Wada M, Tamura A, Takahashi N and Tsukita S: Loss of claudins 2 and 15 from mice causes defects in paracellular Na⁺ flow and nutrient transport in gut and leads to death from malnutrition. Gastroenterology. 144:369–380. 2013. View Article : Google Scholar

Zhou N, Wang H, Liu H, Xue H, Lin F, Meng X, Liang A, Zhao Z, Liu Y and Qian H: MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer. J Exp Clin Cancer Res. 34:1572015. View Article : Google Scholar : PubMed/NCBI

Zheng X, Fan X, Fu B, Zheng M, Zhang A, Zhong K, Yan J, Sun R, Tian Z and Wei H: EpCAM inhibition sensitizes chemo-resistant leukemia to immune surveillance. Cancer Res. 77:482–493. 2017. View Article : Google Scholar

Patriarca C, Macchi RM, Marschner AK and Mellstedt H: Epithelial cell adhesion molecule expression (CD326) in cancer: A short review. Cancer Treat Rev. 38:68–75. 2012. View Article : Google Scholar

Wang MH, Sun R, Zhou XM, Zhang MY, Lu JB, Yang Y, Zeng LS, Yang XZ, Shi L, Xiao RW, et al: Epithelial cell adhesion molecule overexpression regulates epithelial-mesenchymal transition, stemness and metastasis of nasopharyngeal carcinoma cells via the PTEN/AKT/mTOR pathway. Cell Death Dis. 9:22018. View Article : Google Scholar : PubMed/NCBI

Denzel S, Maetzel D, Mack B, Eggert C, Bärr G and Gires O: Initial activation of EpCAM cleavage via cell-to-cell contact. BMC Cancer. 9:4022009. View Article : Google Scholar : PubMed/NCBI

Xiang D, Shigdar S, Bean AG, Bruce M, Yang W, Mathesh M, Wang T, Yin W, Tran PH, Al Shamaileh H, et al: Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery. Theranostics. 7:4071–4086. 2017. View Article : Google Scholar : PubMed/NCBI

Hoe SLL, Tan LP, Abdul Aziz N, Liew K, Teow SY, Abdul Razak FR, Chin YM, Mohamed Shahrehan NA, Chu TL, Mohd Kornain NK, et al: CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma. Sci Rep. 7:123722017. View Article : Google Scholar : PubMed/NCBI

Choi YJ, Park SJ, Park YS, Park HS, Yang KM and Heo K: EpCAM peptide-primed dendritic cell vaccination confers significant anti-tumor immunity in hepatocellular carcinoma cells. PLos One. 13:e01906382018. View Article : Google Scholar : PubMed/NCBI

Hwang EY, Yu CH, Cheng SJ, Chang JY, Chen HM and Chiang CP: Decreased expression of Ep-CAM protein is significantly associated with the progression and prognosis of oral squamous cell carcinomas in Taiwan. J Oral Pathol Med. 38:87–93. 2009. View Article : Google Scholar

Gosens MJ, Van Kempen LC, Van de Velde CJ, Van Krieken JH and Nagtegaal ID: Loss of membranous Ep-CAM in budding colorectal carcinoma cells. Mod Pathol. 20:221–232. 2007. View Article : Google Scholar : PubMed/NCBI

Wen KC, Sung PL, Chou YT, Pan CM, Wang PH, Lee OK and Wu CW: The role of EpCAM in tumor progression and the clinical prognosis of endometrial carcinoma. Gynecol Oncol. 148:383–392. 2018. View Article : Google Scholar

Maloy KJ and Powrie F: Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 474:298–306. 2011. View Article : Google Scholar : PubMed/NCBI

Kaser A, Zeissig S and Blumberg RS: Inflammatory bowel disease. Annu Rev Immunol. 28:573–621. 2010. View Article : Google Scholar : PubMed/NCBI

Mankertz J and Schulzke JD: Altered permeability in inflammatory bowel disease: Pathophysiology and clinical implications. Curr Opin Gastroenterol. 23:379–383. 2007. View Article : Google Scholar : PubMed/NCBI

Welcker K, Martin A, Kölle P, Siebeck M and Gross M: Increased intestinal permeability in patients with inflammatory bowel disease. Eur J Med Res. 9:456–460. 2004.PubMed/NCBI

Doğan A, Wang ZD and Spencer J: E-cadherin expression in intestinal epithelium. J Clin Pathol. 48:143–146. 1995. View Article : Google Scholar : PubMed/NCBI

Gassler N, Rohr C, Schneider A, Kartenbeck J, Bach A, Obermüller N, Otto HF and Autschbach F: Inflammatory bowel disease is associated with changes of enterocytic junctions. Am J Physiol Gastrointest Liver Physiol. 281:G216–G228. 2001. View Article : Google Scholar : PubMed/NCBI

Jankowski JA, Bedford FK, Boulton RA, Cruickshank N, Hall C, Elder J, Allan R, Forbes A, Kim YS, Wright NA and Sanders DS: Alterations in classical cadherins associated with progression in ulcerative and Crohn's colitis. Lab Invest. 78:1155–1167. 1998.PubMed/NCBI

Karayiannakis AJ, Syrigos KN, Efstathiou J, Valizadeh A, Noda M, Playford RJ, Kmiot W and Pignatelli M: Expression of catenins and E-cadherin during epithelial restitution in inflammatory bowel disease. J Pathol. 185:413–418. 1998. View Article : Google Scholar : PubMed/NCBI

Kucharzik T, Walsh SV, Chen J, Parkos CA and Nusrat A: Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. Am J Pathol. 159:2001–2009. 2001. View Article : Google Scholar : PubMed/NCBI

Jiang L, Shen Y, Guo D, Yang D, Liu J, Fei X, Yang Y, Zhang B, Lin Z, Yang F, et al: EpCAM-dependent extracellular vesicles from intestinal epithelial cells maintain intestinal tract immune balance. Nat Commun. 7:130452016. View Article : Google Scholar : PubMed/NCBI

Tanaka H, Takechi M, Kiyonari H, Shioi G, Tamura A and Tsukita S: Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice. Gut. 64:1529–1538. 2015. View Article : Google Scholar : PubMed/NCBI

Sherman PM, Mitchell DJ and Cutz E: Neonatal enteropathies: Defining the causes of protracted diarrhea of infancy. J Pediatr Gastroenterol Nutr. 38:16–26. 2004. View Article : Google Scholar

Ranganathan S, Schmitt LA and Sindhi R: Tufting enteropathy revisited: The utility of MOC31 (EpCAM) immunohisto-chemistry in diagnosis. Am J Surg Pathol. 38:265–272. 2014. View Article : Google Scholar : PubMed/NCBI

Khounlotham M, Kim W, Peatman E, Nava P, Medina-Contreras O, Addis C, Koch S, Fournier B, Nusrat A, Denning TL and Parkos CA: Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis. Immunity. 37:563–573. 2012. View Article : Google Scholar : PubMed/NCBI

Song Y, Liu C, Liu X, Trottier J, Beaudoin M, Zhang L, Pope C, Peng G, Barbier O, Zhong X, et al: H19 promotes cholestatic liver fibrosis by preventing ZEB1-mediated inhibition of epithelial cell adhesion molecule. Hepatology. 66:1183–1196. 2017. View Article : Google Scholar : PubMed/NCBI

Zen Y, Vara R, Portmann B and Hadzic N: Childhood hepatocellular carcinoma: A clinicopathological study of 12 cases with special reference to EpCAM. Histopathology. 64:671–682. 2014. View Article : Google Scholar

Ueno M, Lee LK, Chhabra A, Kim YJ, Sasidharan R, Van Handel B, Wang Y, Kamata M, Kamran P, Sereti KI, et al: c-Met-dependent multipotent labyrinth trophoblast progenitors establish placental exchange interface. Dev Cell. 27:373–386. 2013. View Article : Google Scholar : PubMed/NCBI

Nakaya Y and Sheng G: EMT in developmental morphogenesis. Cancer Lett. 341:9–15. 2013. View Article : Google Scholar : PubMed/NCBI

Han Y, Mu Y, Li X, Xu P, Tong J, Liu Z, Ma T, Zeng G, Yang S, Du J and Meng A: Grhl2 deficiency impairs otic development and hearing ability in a zebrafish model of the progressive dominant hearing loss DFNA28. Hum Mol Genet. 20:3213–3226. 2011. View Article : Google Scholar : PubMed/NCBI

Al-Mayouf SM, Alswaied N, Alkuraya FS, Almehaidib A and Faqih M: Tufting enteropathy and chronic arthritis: A newly recognized association with a novel EpCAM gene mutation. J Pediatr Gastroenterol Nutr. 49:642–644. 2009. View Article : Google Scholar : PubMed/NCBI

Bird LM, Sivagnanam M, Taylor S and Newbury RO: A new syndrome of tufting enteropathy and choanal atresia, with ophthalmologic, hematologic and hair abnormalities. Clin Dysmorphol. 16:211–221. 2007. View Article : Google Scholar : PubMed/NCBI