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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...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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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. |
format | Text |
id | pubmed-2582886 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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