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p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression

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...

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Autores principales: Soto, Edwin, Yanagisawa, Masahiro, Marlow, Laura A., Copland, John A., Perez, Edith A., Anastasiadis, Panos Z.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582886/
https://www.ncbi.nlm.nih.gov/pubmed/19015320
http://dx.doi.org/10.1083/jcb.200805113
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author Soto, Edwin
Yanagisawa, Masahiro
Marlow, Laura A.
Copland, John A.
Perez, Edith A.
Anastasiadis, Panos Z.
author_facet Soto, Edwin
Yanagisawa, Masahiro
Marlow, Laura A.
Copland, John A.
Perez, Edith A.
Anastasiadis, Panos Z.
author_sort Soto, Edwin
collection PubMed
description 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.
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spelling pubmed-25828862009-05-18 p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression Soto, Edwin Yanagisawa, Masahiro Marlow, Laura A. Copland, John A. Perez, Edith A. Anastasiadis, Panos Z. J Cell Biol Research Articles 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. The Rockefeller University Press 2008-11-17 /pmc/articles/PMC2582886/ /pubmed/19015320 http://dx.doi.org/10.1083/jcb.200805113 Text en © 2008 Soto et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Soto, Edwin
Yanagisawa, Masahiro
Marlow, Laura A.
Copland, John A.
Perez, Edith A.
Anastasiadis, Panos Z.
p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression
title p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression
title_full p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression
title_fullStr p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression
title_full_unstemmed p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression
title_short p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression
title_sort p120 catenin induces opposing effects on tumor cell growth depending on e-cadherin expression
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582886/
https://www.ncbi.nlm.nih.gov/pubmed/19015320
http://dx.doi.org/10.1083/jcb.200805113
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