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J Cell Biol. 1994 Dec 2; 127(6): 2061–2069.
doi: 10.1083/jcb.127.6.2061
PMCID: PMC2120290
PMID: 7806582

E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton

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Abstract

beta-Catenin is involved in the formation of adherens junctions of mammalian epithelia. It interacts with the cell adhesion molecule E- cadherin and also with the tumor suppressor gene product APC, and the Drosophila homologue of beta-catenin, armadillo, mediates morphogenetic signals. We demonstrate here that E-cadherin and APC directly compete for binding to the internal, armadillo-like repeats of beta-catenin; the NH2-terminal domain of beta-catenin mediates the interaction of the alternative E-cadherin and APC complexes to the cytoskeleton by binding to alpha-catenin. Plakoglobin (gamma-catenin), which is structurally related to beta-catenin, mediates identical interactions. We thus show that the APC tumor suppressor gene product forms strikingly similar associations as found in cell junctions and suggest that beta-catenin and plakoglobin are central regulators of cell adhesion, cytoskeletal interaction, and tumor suppression.

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Selected References

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  • Becker KF, Atkinson MJ, Reich U, Becker I, Nekarda H, Siewert JR, Höfler H. E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 1994 Jul 15;54(14):3845–3852. [PubMed] [Google Scholar]
  • Behrens J, Mareel MM, Van Roy FM, Birchmeier W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol. 1989 Jun;108(6):2435–2447. [PMC free article] [PubMed] [Google Scholar]
  • Behrens J, Vakaet L, Friis R, Winterhager E, Van Roy F, Mareel MM, Birchmeier W. Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J Cell Biol. 1993 Feb;120(3):757–766. [PMC free article] [PubMed] [Google Scholar]
  • Bejsovec A, Wieschaus E. Segment polarity gene interactions modulate epidermal patterning in Drosophila embryos. Development. 1993 Oct;119(2):501–517. [PubMed] [Google Scholar]
  • Birchmeier W, Weidner KM, Hülsken J, Behrens J. Molecular mechanisms leading to cell junction (cadherin) deficiency in invasive carcinomas. Semin Cancer Biol. 1993 Aug;4(4):231–239. [PubMed] [Google Scholar]
  • Boller K, Vestweber D, Kemler R. Cell-adhesion molecule uvomorulin is localized in the intermediate junctions of adult intestinal epithelial cells. J Cell Biol. 1985 Jan;100(1):327–332. [PMC free article] [PubMed] [Google Scholar]
  • Bradley RS, Cowin P, Brown AM. Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion. J Cell Biol. 1993 Dec;123(6 Pt 2):1857–1865. [PMC free article] [PubMed] [Google Scholar]
  • Butz S, Stappert J, Weissig H, Kemler R. Plakoglobin and beta-catenin: distinct but closely related. Science. 1992 Aug 21;257(5073):1142–1144. [PubMed] [Google Scholar]
  • Cowin P, Kapprell HP, Franke WW, Tamkun J, Hynes RO. Plakoglobin: a protein common to different kinds of intercellular adhering junctions. Cell. 1986 Sep 26;46(7):1063–1073. [PubMed] [Google Scholar]
  • Evan GI, Lewis GK, Ramsay G, Bishop JM. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985 Dec;5(12):3610–3616. [PMC free article] [PubMed] [Google Scholar]
  • Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. [PubMed] [Google Scholar]
  • Franke WW, Goldschmidt MD, Zimbelmann R, Mueller HM, Schiller DL, Cowin P. Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4027–4031. [PMC free article] [PubMed] [Google Scholar]
  • Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Löchner D, Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. [PMC free article] [PubMed] [Google Scholar]
  • Garrod DR. Desmosomes and hemidesmosomes. Curr Opin Cell Biol. 1993 Feb;5(1):30–40. [PubMed] [Google Scholar]
  • Groden J, Thliveris A, Samowitz W, Carlson M, Gelbert L, Albertsen H, Joslyn G, Stevens J, Spirio L, Robertson M, et al. Identification and characterization of the familial adenomatous polyposis coli gene. Cell. 1991 Aug 9;66(3):589–600. [PubMed] [Google Scholar]
  • Hamaguchi M, Matsuyoshi N, Ohnishi Y, Gotoh B, Takeichi M, Nagai Y. p60v-src causes tyrosine phosphorylation and inactivation of the N-cadherin-catenin cell adhesion system. EMBO J. 1993 Jan;12(1):307–314. [PMC free article] [PubMed] [Google Scholar]
  • Hartmann G, Naldini L, Weidner KM, Sachs M, Vigna E, Comoglio PM, Birchmeier W. A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11574–11578. [PMC free article] [PubMed] [Google Scholar]
  • Herrenknecht K, Ozawa M, Eckerskorn C, Lottspeich F, Lenter M, Kemler R. The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9156–9160. [PMC free article] [PubMed] [Google Scholar]
  • Hinck L, Nelson WJ, Papkoff J. Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin. J Cell Biol. 1994 Mar;124(5):729–741. [PMC free article] [PubMed] [Google Scholar]
  • Hinck L, Näthke IS, Papkoff J, Nelson WJ. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol. 1994 Jun;125(6):1327–1340. [PMC free article] [PubMed] [Google Scholar]
  • Hirano S, Kimoto N, Shimoyama Y, Hirohashi S, Takeichi M. Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization. Cell. 1992 Jul 24;70(2):293–301. [PubMed] [Google Scholar]
  • Kintner C. Regulation of embryonic cell adhesion by the cadherin cytoplasmic domain. Cell. 1992 Apr 17;69(2):225–236. [PubMed] [Google Scholar]
  • Kinzler KW, Nilbert MC, Su LK, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, et al. Identification of FAP locus genes from chromosome 5q21. Science. 1991 Aug 9;253(5020):661–665. [PubMed] [Google Scholar]
  • Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science. 1991 Aug 9;253(5020):665–669. [PubMed] [Google Scholar]
  • Knudsen KA, Wheelock MJ. Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin. J Cell Biol. 1992 Aug;118(3):671–679. [PMC free article] [PubMed] [Google Scholar]
  • Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. [PubMed] [Google Scholar]
  • McCrea PD, Turck CW, Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science. 1991 Nov 29;254(5036):1359–1361. [PubMed] [Google Scholar]
  • McCrea PD, Brieher WM, Gumbiner BM. Induction of a secondary body axis in Xenopus by antibodies to beta-catenin. J Cell Biol. 1993 Oct;123(2):477–484. [PMC free article] [PubMed] [Google Scholar]
  • McNeill H, Ozawa M, Kemler R, Nelson WJ. Novel function of the cell adhesion molecule uvomorulin as an inducer of cell surface polarity. Cell. 1990 Jul 27;62(2):309–316. [PubMed] [Google Scholar]
  • Munemitsu S, Souza B, Müller O, Albert I, Rubinfeld B, Polakis P. The APC gene product associates with microtubules in vivo and promotes their assembly in vitro. Cancer Res. 1994 Jul 15;54(14):3676–3681. [PubMed] [Google Scholar]
  • Nagafuchi A, Shirayoshi Y, Okazaki K, Yasuda K, Takeichi M. Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA. Nature. 1987 Sep 24;329(6137):341–343. [PubMed] [Google Scholar]
  • Nagafuchi A, Takeichi M. Cell binding function of E-cadherin is regulated by the cytoplasmic domain. EMBO J. 1988 Dec 1;7(12):3679–3684. [PMC free article] [PubMed] [Google Scholar]
  • Nagafuchi A, Takeichi M, Tsukita S. The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Cell. 1991 May 31;65(5):849–857. [PubMed] [Google Scholar]
  • Näthke IS, Hinck L, Swedlow JR, Papkoff J, Nelson WJ. Defining interactions and distributions of cadherin and catenin complexes in polarized epithelial cells. J Cell Biol. 1994 Jun;125(6):1341–1352. [PMC free article] [PubMed] [Google Scholar]
  • Oda T, Kanai Y, Oyama T, Yoshiura K, Shimoyama Y, Birchmeier W, Sugimura T, Hirohashi S. E-cadherin gene mutations in human gastric carcinoma cell lines. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1858–1862. [PMC free article] [PubMed] [Google Scholar]
  • Ozawa M, Baribault H, Kemler R. The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. EMBO J. 1989 Jun;8(6):1711–1717. [PMC free article] [PubMed] [Google Scholar]
  • Ozawa M, Ringwald M, Kemler R. Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4246–4250. [PMC free article] [PubMed] [Google Scholar]
  • Peifer M, Wieschaus E. The segment polarity gene armadillo encodes a functionally modular protein that is the Drosophila homolog of human plakoglobin. Cell. 1990 Dec 21;63(6):1167–1176. [PubMed] [Google Scholar]
  • Peifer M, McCrea PD, Green KJ, Wieschaus E, Gumbiner BM. The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties. J Cell Biol. 1992 Aug;118(3):681–691. [PMC free article] [PubMed] [Google Scholar]
  • Peifer M, Berg S, Reynolds AB. A repeating amino acid motif shared by proteins with diverse cellular roles. Cell. 1994 Mar 11;76(5):789–791. [PubMed] [Google Scholar]
  • Reichmann E, Schwarz H, Deiner EM, Leitner I, Eilers M, Berger J, Busslinger M, Beug H. Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion. Cell. 1992 Dec 24;71(7):1103–1116. [PubMed] [Google Scholar]
  • Risinger JI, Berchuck A, Kohler MF, Boyd J. Mutations of the E-cadherin gene in human gynecologic cancers. Nat Genet. 1994 May;7(1):98–102. [PubMed] [Google Scholar]
  • Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B, et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2. Nature. 1993 Jun 10;363(6429):515–521. [PubMed] [Google Scholar]
  • Rubinfeld B, Souza B, Albert I, Müller O, Chamberlain SH, Masiarz FR, Munemitsu S, Polakis P. Association of the APC gene product with beta-catenin. Science. 1993 Dec 10;262(5140):1731–1734. [PubMed] [Google Scholar]
  • Shibamoto S, Hayakawa M, Takeuchi K, Hori T, Oku N, Miyazawa K, Kitamura N, Takeichi M, Ito F. Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells. Cell Adhes Commun. 1994 Jan;1(4):295–305. [PubMed] [Google Scholar]
  • Smith KJ, Johnson KA, Bryan TM, Hill DE, Markowitz S, Willson JK, Paraskeva C, Petersen GM, Hamilton SR, Vogelstein B, et al. The APC gene product in normal and tumor cells. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2846–2850. [PMC free article] [PubMed] [Google Scholar]
  • Smith KJ, Levy DB, Maupin P, Pollard TD, Vogelstein B, Kinzler KW. Wild-type but not mutant APC associates with the microtubule cytoskeleton. Cancer Res. 1994 Jul 15;54(14):3672–3675. [PubMed] [Google Scholar]
  • Sokol S, Christian JL, Moon RT, Melton DA. Injected Wnt RNA induces a complete body axis in Xenopus embryos. Cell. 1991 Nov 15;67(4):741–752. [PubMed] [Google Scholar]
  • Su LK, Vogelstein B, Kinzler KW. Association of the APC tumor suppressor protein with catenins. Science. 1993 Dec 10;262(5140):1734–1737. [PubMed] [Google Scholar]
  • Trofatter JA, MacCollin MM, Rutter JL, Murrell JR, Duyao MP, Parry DM, Eldridge R, Kley N, Menon AG, Pulaski K, et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell. 1993 Mar 12;72(5):791–800. [PubMed] [Google Scholar]
  • Tsukita S, Tsukita S, Nagafuchi A, Yonemura S. Molecular linkage between cadherins and actin filaments in cell-cell adherens junctions. Curr Opin Cell Biol. 1992 Oct;4(5):834–839. [PubMed] [Google Scholar]
  • Tsukita S, Itoh M, Nagafuchi A, Yonemura S, Tsukita S. Submembranous junctional plaque proteins include potential tumor suppressor molecules. J Cell Biol. 1993 Dec;123(5):1049–1053. [PMC free article] [PubMed] [Google Scholar]
  • van Leeuwen F, Samos CH, Nusse R. Biological activity of soluble wingless protein in cultured Drosophila imaginal disc cells. Nature. 1994 Mar 24;368(6469):342–344. [PubMed] [Google Scholar]
  • Vestweber D, Kemler R. Identification of a putative cell adhesion domain of uvomorulin. EMBO J. 1985 Dec 16;4(13A):3393–3398. [PMC free article] [PubMed] [Google Scholar]
  • 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 Jul 12;66(1):107–119. [PubMed] [Google Scholar]
  • Weidner KM, Behrens J, Vandekerckhove J, Birchmeier W. Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells. J Cell Biol. 1990 Nov;111(5 Pt 1):2097–2108. [PMC free article] [PubMed] [Google Scholar]
  • Woods DF, Bryant PJ. The discs-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell. 1991 Aug 9;66(3):451–464. [PubMed] [Google Scholar]
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