Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Tianzhen WangEmail author
  • Xiaobo Li
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101598


 Arc-1;  CD324;  CDHE;  ECAD;  LCAM;  UVO

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...
This is a preview of subscription content, log in to check access.


  1. Anastasiadis PZ, Reynolds AB. Regulation of Rho GTPases by p120-catenin. Curr Opin Cell Biol. 2001;13:604–10.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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.PubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefPubMedGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar
  31. 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.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PathologyHarbin Medical UniversityHarbinChina
  2. 2.Center of Translational MedicineHarbin Medical UniversityHarbinChina