P120 Catenin Induces Opposing Effects on Tumor Cell Growth Depending on E-cadherin Expression

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2008 Nov 19

PMID 19015320

Citations 52

Authors

Edwin Soto

Masahiro Yanagisawa

Laura A Marlow

John A Copland

Edith A Perez

Panos Z Anastasiadis

Affiliations

Soon will be listed here.

Abstract

p120 catenin regulates the activity of the Rho family guanosine triphosphatases (including RhoA and Rac1) in an adhesion-dependent manner. Through this action, p120 promotes a sessile cellular phenotype when associated with epithelial cadherin (E-cadherin) or a motile phenotype when associated with mesenchymal cadherins. In this study, we show that p120 also exerts significant and diametrically opposing effects on tumor cell growth depending on E-cadherin expression. Endogenous p120 acts to stabilize E-cadherin complexes and to actively promote the tumor-suppressive function of E-cadherin, potently inhibiting Ras activation. Upon E-cadherin loss during tumor progression, the negative regulation of Ras is relieved; under these conditions, endogenous p120 promotes transformed cell growth both in vitro and in vivo by activating a Rac1-mitogen-activated protein kinase signaling pathway normally activated by the adhesion of cells to the extracellular matrix. These data indicate that both E-cadherin and p120 are important regulators of tumor cell growth and imply roles for both proteins in chemoresistance and targeted therapeutics.

Citing Articles

Functions of p120-catenin in physiology and diseases.

Jin X, Lin T, Wang Y, Li X, Yang Y Front Mol Biosci. 2024; 11:1486576.

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