E-N-cadherin Heterodimers Define Novel Adherens Junctions Connecting Endoderm-derived Cells

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2011 Nov 23

PMID 22105347

Citations 33

Authors

Beate K Straub

Steffen Rickelt

Ralf Zimbelmann

Christine Grund

Caecilia Kuhn

Marcus Iken

Michael Ott

Peter Schirmacher

Werner W Franke

Affiliations

Soon will be listed here.

Abstract

Intercellular junctions play a pivotal role in tissue development and function and also in tumorigenesis. In epithelial cells, decrease or loss of E-cadherin, the hallmark molecule of adherens junctions (AJs), and increase of N-cadherin are widely thought to promote carcinoma progression and metastasis. In this paper, we show that this "cadherin switch" hypothesis does not hold for diverse endoderm-derived cells and cells of tumors derived from them. We show that the cadherins in a major portion of AJs in these cells can be chemically cross-linked in E-N heterodimers. We also show that cells possessing E-N heterodimer AJs can form semistable hemihomotypic AJs with purely N-cadherin-based AJs of mesenchymally derived cells, including stroma cells. We conclude that these heterodimers are the major AJ constituents of several endoderm-derived tissues and tumors and that the prevailing concept of antagonistic roles of these two cadherins in developmental and tumor biology has to be reconsidered.

Citing Articles

A five-plex Hepatic Oncochip reveals EMT triplet correlated with BAP31 in liver cancer.

Kong Y, Zhuang T, Ding X, Cai S, Ding W, Zhang X Front Cell Dev Biol. 2025; 12():1478444.

PMID: 39834395 PMC: 11743502. DOI: 10.3389/fcell.2024.1478444.

Gastric-Type Expression Signature in Hepatocellular Carcinoma.

Szodorai R, Banias L, Kovalszky I, Dezso K, Kovacs Z, Gurzu S Int J Mol Sci. 2024; 25(12).

PMID: 38928294 PMC: 11203738. DOI: 10.3390/ijms25126588.

The journey of a generation: advances and promises in the study of primordial germ cell migration.

Barton L, Roa-de la Cruz L, Lehmann R, Lin B Development. 2024; 151(7).

PMID: 38607588 PMC: 11165723. DOI: 10.1242/dev.201102.

Neural crest cell-placodal neuron interactions are mediated by Cadherin-7 and N-cadherin during early chick trigeminal ganglion assembly.

Halmi C, Wu C, Taneyhill L F1000Res. 2023; 11:741.

PMID: 36128560 PMC: 9475207. DOI: 10.12688/f1000research.122686.2.

Constitutive Occurrence of E:N-cadherin Heterodimers in Adherens Junctions of Hepatocytes and Derived Tumors.

Gerber T, Ridder D, Schindeldecker M, Weinmann A, Duret D, Breuhahn K Cells. 2022; 11(16).

PMID: 36010583 PMC: 9406782. DOI: 10.3390/cells11162507.

References

Leitner A, Walzthoeni T, Kahraman A, Herzog F, Rinner O, Beck M . Probing native protein structures by chemical cross-linking, mass spectrometry, and bioinformatics. Mol Cell Proteomics. 2010; 9(8):1634-49. PMC: 2938055. DOI: 10.1074/mcp.R000001-MCP201. View

Sinz A . Chemical cross-linking and mass spectrometry for mapping three-dimensional structures of proteins and protein complexes. J Mass Spectrom. 2003; 38(12):1225-37. DOI: 10.1002/jms.559. View

Alexandrova K, Griesel C, Barthold M, Heuft H, Ott M, Winkler M . Large-scale isolation of human hepatocytes for therapeutic application. Cell Transplant. 2006; 14(10):845-53. DOI: 10.3727/000000005783982530. View

Yilmaz M, Christofori G . EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009; 28(1-2):15-33. DOI: 10.1007/s10555-008-9169-0. View

de Beco S, Gueudry C, Amblard F, Coscoy S . Endocytosis is required for E-cadherin redistribution at mature adherens junctions. Proc Natl Acad Sci U S A. 2009; 106(17):7010-5. PMC: 2678428. DOI: 10.1073/pnas.0811253106. View

Birchmeier W, Weidner K, Behrens J . Molecular mechanisms leading to loss of differentiation and gain of invasiveness in epithelial cells. J Cell Sci Suppl. 1993; 17:159-64. DOI: 10.1242/jcs.1993.supplement_17.23. View

Shan W, Tanaka H, Phillips G, Arndt K, Yoshida M, Colman D . Functional cis-heterodimers of N- and R-cadherins. J Cell Biol. 2000; 148(3):579-90. PMC: 2174798. DOI: 10.1083/jcb.148.3.579. View

Kim J, Islam S, Kim Y, Prudoff R, Sass K, Wheelock M . N-Cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility. J Cell Biol. 2000; 151(6):1193-206. PMC: 2190584. DOI: 10.1083/jcb.151.6.1193. View

Mareel M, Behrens J, Birchmeier W, De Bruyne G, Vleminckx K, Hoogewijs A . Down-regulation of E-cadherin expression in Madin Darby canine kidney (MDCK) cells inside tumors of nude mice. Int J Cancer. 1991; 47(6):922-8. DOI: 10.1002/ijc.2910470623. View

10.

Niessen C, Gumbiner B . Cadherin-mediated cell sorting not determined by binding or adhesion specificity. J Cell Biol. 2002; 156(2):389-399. PMC: 2199232. DOI: 10.1083/jcb.200108040. View

11.

Seglen P . Hepatocyte suspensions and cultures as tools in experimental carcinogenesis. J Toxicol Environ Health. 1979; 5(2-3):551-60. DOI: 10.1080/15287397909529766. View

12.

Libusova L, Stemmler M, Hierholzer A, Schwarz H, Kemler R . N-cadherin can structurally substitute for E-cadherin during intestinal development but leads to polyp formation. Development. 2010; 137(14):2297-305. DOI: 10.1242/dev.048488. View

13.

Ihara A, Koizumi H, Hashizume R, Uchikoshi T . Expression of epithelial cadherin and alpha- and beta-catenins in nontumoral livers and hepatocellular carcinomas. Hepatology. 1996; 23(6):1441-7. DOI: 10.1053/jhep.1996.v23.pm0008675162. View

14.

Katsamba P, Carroll K, Ahlsen G, Bahna F, Vendome J, Posy S . Linking molecular affinity and cellular specificity in cadherin-mediated adhesion. Proc Natl Acad Sci U S A. 2009; 106(28):11594-9. PMC: 2710653. DOI: 10.1073/pnas.0905349106. View

15.

Theard D, Steiner M, Kalicharan D, Hoekstra D, van Ijzendoorn S . Cell polarity development and protein trafficking in hepatocytes lacking E-cadherin/beta-catenin-based adherens junctions. Mol Biol Cell. 2007; 18(6):2313-21. PMC: 1877101. DOI: 10.1091/mbc.e06-11-1040. View

16.

Straub B, Stoeffel P, Heid H, Zimbelmann R, Schirmacher P . Differential pattern of lipid droplet-associated proteins and de novo perilipin expression in hepatocyte steatogenesis. Hepatology. 2008; 47(6):1936-46. DOI: 10.1002/hep.22268. View

17.

Foty R, Steinberg M . The differential adhesion hypothesis: a direct evaluation. Dev Biol. 2005; 278(1):255-63. DOI: 10.1016/j.ydbio.2004.11.012. View

18.

Cavallaro U, Christofori G . Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nat Rev Cancer. 2004; 4(2):118-32. DOI: 10.1038/nrc1276. View

19.

Zhang Y, Sivasankar S, Nelson W, Chu S . Resolving cadherin interactions and binding cooperativity at the single-molecule level. Proc Natl Acad Sci U S A. 2008; 106(1):109-14. PMC: 2629205. DOI: 10.1073/pnas.0811350106. View

20.

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View