A reaction-diffusion model of the cadherin-catenin system: A possible mechanism for contact inhibition and implications for tumorigenesis

Markus Basan, Timon Idema, Martin Lenz*, Jean François Joanny, Thomas Risler

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

16 Citations (Scopus)

Abstract

Contact inhibition is the process by which cells switch from a motile growing state to a passive and stabilized state upon touching their neighbors. When two cells touch, an adhesion link is created between them by means of transmembrane E-cadherin proteins. Simultaneously, their actin filaments stop polymerizing in the direction perpendicular to the membrane and reorganize to create an apical belt that colocalizes with the adhesion links. Here, we propose a detailed quantitative model of the role of cytoplasmic β-catenin and a-catenin proteins in this process, treated as a reaction-diffusion system. Upon cell-cell contact the concentration in α-catenin dinners increases, inhibiting actin branching and thereby reducing cellular motility and expansion pressure. This model provides a mechanism for contact inhibition that could explain previously unrelated experimental findings on the role played by E-cadherin, β-catenin, and α-catenin in the cellular phenotype and in tumorigenesis. In particular, we address the effect of a knockout of the adenomatous polyposis coli tumor suppressor gene. Potential direct tests of our model are discussed.

Original languageEnglish
Pages (from-to)2770-2779
Number of pages10
JournalBiophysical Journal
Volume98
Issue number12
DOIs
Publication statusPublished - 16 Jun 2010

Bibliographical note

Funding Information:
We thank F. Amblard, J. Whitehead, E. Farge, and C. Storm for a critical reading of the manuscript and many helpful discussions. T.I. acknowledges financial support from the Foundation for Fundamental Research on Matter of the Netherlands Organisation for Scientific Research (NWO-FOM) within the program on Material Properties of Biological Assemblies (grant FOM-L2601M).

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

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