A Reaction-Diffusion Model of the Cadherin-Catenin System: A Possible Mechanism for Contact Inhibition and Implications for Tumorigenesis

TL;DR

This paper presents a quantitative reaction-diffusion model explaining contact inhibition via cadherin-catenin interactions, linking cellular adhesion to motility regulation and tumorigenesis, with implications for understanding tumor suppressor gene effects.

Contribution

It introduces a detailed reaction-diffusion model of the cadherin-catenin system as a mechanism for contact inhibition and tumor suppression.

Findings

Increased $oldsymbol{eta}$-catenin and $oldsymbol{eta}$-catenin concentrations inhibit actin polymerization.

The model links cell adhesion molecules to cellular motility regulation.

It suggests a mechanism by which tumor suppressor gene knockout affects contact inhibition.

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 the cytoplasmic $\beta$-catenin and $\alpha$-catenin proteins in this process, treated as a reaction-diffusion system. Upon cell-cell contact, the concentration in $\alpha$-catenin dimers 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, $\beta$-catenin and $\alpha$-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.