Historical Background
E-cadherin is a member of the cadherin family, a family of transmembrane glycoproteins responsible for calcium-dependent cell adhesion that are the key structural components of adherens junctions (AJs). E-cadherin is encoded by CDH1 gene that localizes at 16q22.1 and composes of 18 exons. E-cadherin protein presents in epithelial tissues and composes of a single-pass transmembrane region, a cytoplasmic region, and an ectoregion that consisted of five tandemly repeated subdomains, each harboring two conserved regions representing the putative calcium binding sites (van Roy and Berx 2008). The extracellular domain of E-cadherin within one cell formed X-shaped cis dimmers, and the trans dimmer “Zipper” formed between multiple X-shaped cis dimmers of adjacent cells is the molecular basis of cell-cell adhesion (van Roy and Berx 2008). The intracellular domain of E-cadherin contains a highly phosphorylated region vital to...
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Anastasiadis PZ, Reynolds AB. Regulation of Rho GTPases by p120-catenin. Curr Opin Cell Biol. 2001;13:604–10.
Benham-Pyle BW, Pruitt BL, Nelson WJ. Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and beta-catenin activation to drive cell cycle entry. Science. 2015;348:1024–7. https://doi.org/10.1126/science.aaa4559.
Bryant DM, Wylie FG, Stow JL. Regulation of endocytosis, nuclear translocation, and signaling of fibroblast growth factor receptor 1 by E-cadherin. Mol Biol Cell. 2005;16:14–23. https://doi.org/10.1091/mbc.E04-09-0845.
Coniglio SJ, Jou TS, Symons M. Rac1 protects epithelial cells against anoikis. J Biol Chem. 2001;276:28113–20. https://doi.org/10.1074/jbc.M102299200.
Cowell CF, Yan IK, Eiseler T, Leightner AC, Doppler H, Storz P. Loss of cell-cell contacts induces NF-kappaB via RhoA-mediated activation of protein kinase D1. J Cell Biochem. 2009;106:714–28. https://doi.org/10.1002/jcb.22067.
De Santis G, Miotti S, Mazzi M, Canevari S, Tomassetti A. E-cadherin directly contributes to PI3K/AKT activation by engaging the PI3K-p85 regulatory subunit to adherens junctions of ovarian carcinoma cells. Oncogene. 2009;28:1206–17. https://doi.org/10.1038/onc.2008.470.
Du W, Liu X, Fan G, Zhao X, Sun Y, Wang T, et al. From cell membrane to the nucleus: an emerging role of E-cadherin in gene transcriptional regulation. J Cell Mol Med. 2014;18:1712–9. https://doi.org/10.1111/jcmm.12340.
Fedor-Chaiken M, Hein PW, Stewart JC, Brackenbury R, Kinch MS. E-cadherin binding modulates EGF receptor activation. Cell Commun Adhes. 2003;10:105–18.
Ferber EC, Kajita M, Wadlow A, Tobiansky L, Niessen C, Ariga H, et al. A role for the cleaved cytoplasmic domain of E-cadherin in the nucleus. J Biol Chem. 2008;283:12691–700. https://doi.org/10.1074/jbc.M708887200.
Fukumoto Y, Shintani Y, Reynolds AB, Johnson KR, Wheelock MJ. The regulatory or phosphorylation domain of p120 catenin controls E-cadherin dynamics at the plasma membrane. Exp Cell Res. 2008;314:52–67. https://doi.org/10.1016/j.yexcr.2007.07.024.
Hawkins PT, Eguinoa A, Qiu RG, Stokoe D, Cooke FT, Walters R, et al. PDGF stimulates an increase in GTP-Rac via activation of phosphoinositide 3-kinase. Curr Biol. 1995;5:393–403.
Hosking CR, Ulloa F, Hogan C, Ferber EC, Figueroa A, Gevaert K, et al. The transcriptional repressor Glis2 is a novel binding partner for p120 catenin. Mol Biol Cell. 2007;18:1918–27. https://doi.org/10.1091/mbc.E06-10-0941.
Jamora C, DasGupta R, Kocieniewski P, Fuchs E. Links between signal transduction, transcription and adhesion in epithelial bud development. Nature. 2003;422:317–22. https://doi.org/10.1038/nature01458.
Kim SH, Li Z, Sacks DB. E-cadherin-mediated cell-cell attachment activates Cdc42. J Biol Chem. 2000;275:36999–7005. https://doi.org/10.1074/jbc.M003430200.
Kim SW, Park JI, Spring CM, Sater AK, Ji H, Otchere AA, et al. Non-canonical Wnt signals are modulated by the Kaiso transcriptional repressor and p120-catenin. Nat Cell Biol. 2004;6:1212–20. https://doi.org/10.1038/ncb1191.
Kovacs EM, Ali RG, McCormack AJ, Yap AS. E-cadherin homophilic ligation directly signals through Rac and phosphatidylinositol 3-kinase to regulate adhesive contacts. J Biol Chem. 2002;277:6708–18. https://doi.org/10.1074/jbc.M109640200.
Kuphal F, Behrens J. E-cadherin modulates Wnt-dependent transcription in colorectal cancer cells but does not alter Wnt-independent gene expression in fibroblasts. Exp Cell Res. 2006;312:457–67. https://doi.org/10.1016/j.yexcr.2005.11.007.
Kuphal S, Poser I, Jobin C, Hellerbrand C, Bosserhoff AK. Loss of E-cadherin leads to upregulation of NFkappaB activity in malignant melanoma. Oncogene. 2004;23:8509–19. https://doi.org/10.1038/sj.onc.1207831.
Leibfried A, Fricke R, Morgan MJ, Bogdan S, Bellaiche Y. Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis. Curr Biol. 2008;18:1639–48. https://doi.org/10.1016/j.cub.2008.09.063.
McCrea PD, Maher MT, Gottardi CJ. Nuclear signaling from cadherin adhesion complexes. Curr Top Dev Biol. 2015;112:129–96. https://doi.org/10.1016/bs.ctdb.2014.11.018.
Nakagawa M, Fukata M, Yamaga M, Itoh N, Kaibuchi K. Recruitment and activation of Rac1 by the formation of E-cadherin-mediated cell-cell adhesion sites. J Cell Sci. 2001;114:1829–38.
Ochiai A, Akimoto S, Kanai Y, Shibata T, Oyama T, Hirohashi S. c-erbB-2 gene product associates with catenins in human cancer cells. Biochem Biophys Res Commun. 1994;205:73–8. https://doi.org/10.1006/bbrc.1994.2631.
Olson MF, Paterson HF, Marshall CJ. Signals from Ras and Rho GTPases interact to regulate expression of p21Waf1/Cip1. Nature. 1998;394:295–9. https://doi.org/10.1038/28425.
Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008;68:3645–54. https://doi.org/10.1158/0008-5472.can-07-2938.
Orsulic S, Huber O, Aberle H, Arnold S, Kemler R. E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. J Cell Sci. 1999;112(Pt 8):1237–45.
Park JI, Ji H, Jun S, Gu D, Hikasa H, Li L, et al. Frodo links Dishevelled to the p120-catenin/Kaiso pathway: distinct catenin subfamilies promote Wnt signals. Dev Cell. 2006;11:683–95. https://doi.org/10.1016/j.devcel.2006.09.022.
Soto E, Yanagisawa M, Marlow LA, Copland JA, Perez EA, Anastasiadis PZ. p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression. J Cell Biol. 2008;183:737–49. https://doi.org/10.1083/jcb.200805113.
Spring CM, Kelly KF, O’Kelly I, Graham M, Crawford HC, Daniel JM. The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin. Exp Cell Res. 2005;305:253–65. https://doi.org/10.1016/j.yexcr.2005.01.007.
Su YJ, Chang YW, Lin WH, Liang CL, Lee JL. An aberrant nuclear localization of E-cadherin is a potent inhibitor of Wnt/beta-catenin-elicited promotion of the cancer stem cell phenotype. Oncogenesis. 2015;4:e157. https://doi.org/10.1038/oncsis.2015.17.
Tong Z, Chakraborty S, Sung B, Koolwal P, Kaur S, Aggarwal BB, et al. Epidermal growth factor down-regulates the expression of neutrophil gelatinase-associated lipocalin (NGAL) through E-cadherin in pancreatic cancer cells. Cancer. 2011;117:2408–18. https://doi.org/10.1002/cncr.25803.
van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 2008;65:3756–88. https://doi.org/10.1007/s00018-008-8281-1.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Wang, T., Li, X. (2018). E-Cadherin. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101598
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101598
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences