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Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells

Apicobasolateral polarity is a fundamental property of epithelial cells, and its loss is a hallmark of cancer. Integrin-mediated contact with the extracellular matrix defines the basal surface, setting in motion E-cadherin–mediated cell–cell contact, which establishes apicobasolateral polarity. Role...

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Autores principales: Starchenko, Alina, Graves-Deal, Ramona, Yang, Yu-Ping, Li, Cunxi, Zent, Roy, Singh, Bhuminder, Coffey, Robert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426844/
https://www.ncbi.nlm.nih.gov/pubmed/28356422
http://dx.doi.org/10.1091/mbc.E16-12-0852
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author Starchenko, Alina
Graves-Deal, Ramona
Yang, Yu-Ping
Li, Cunxi
Zent, Roy
Singh, Bhuminder
Coffey, Robert J.
author_facet Starchenko, Alina
Graves-Deal, Ramona
Yang, Yu-Ping
Li, Cunxi
Zent, Roy
Singh, Bhuminder
Coffey, Robert J.
author_sort Starchenko, Alina
collection PubMed
description Apicobasolateral polarity is a fundamental property of epithelial cells, and its loss is a hallmark of cancer. Integrin-mediated contact with the extracellular matrix defines the basal surface, setting in motion E-cadherin–mediated cell–cell contact, which establishes apicobasolateral polarity. Role(s) for lateral integrins in this polarization process and the consequences of their disruption are incompletely understood. We show that addition of an integrin β1–activating monoclonal antibody, P4G11, to invasive colorectal cancer cells in three-dimensional type 1 collagen reverts the invasive phenotype and restores apicobasolateral polarity. P4G11 induces clustering of integrin α5β1 at lateral, intercellular surfaces. This leads to deposition and polymerization of fibronectin and recruitment of paxillin to sites of lateral integrin α5β1 clustering and is followed by tight junction formation, as determined by ZO-1 localization. Inducible elimination of integrin α5 abrogates the epithelial-organizing effects of P4G11. In addition, polymerization of fibronectin is required for the effects of P4G11, and addition of polymerized superfibronectin is sufficient to induce tight junction formation and apicobasolateral polarization. In the normal human colon, we show that integrin α5 localizes to the lateral membrane of terminally differentiated colonocytes and that integrin α5 staining may be reduced in colorectal cancer. Thus we propose a novel role for integrin α5β1 in regulating epithelial morphogenesis.
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spelling pubmed-54268442017-07-30 Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells Starchenko, Alina Graves-Deal, Ramona Yang, Yu-Ping Li, Cunxi Zent, Roy Singh, Bhuminder Coffey, Robert J. Mol Biol Cell Articles Apicobasolateral polarity is a fundamental property of epithelial cells, and its loss is a hallmark of cancer. Integrin-mediated contact with the extracellular matrix defines the basal surface, setting in motion E-cadherin–mediated cell–cell contact, which establishes apicobasolateral polarity. Role(s) for lateral integrins in this polarization process and the consequences of their disruption are incompletely understood. We show that addition of an integrin β1–activating monoclonal antibody, P4G11, to invasive colorectal cancer cells in three-dimensional type 1 collagen reverts the invasive phenotype and restores apicobasolateral polarity. P4G11 induces clustering of integrin α5β1 at lateral, intercellular surfaces. This leads to deposition and polymerization of fibronectin and recruitment of paxillin to sites of lateral integrin α5β1 clustering and is followed by tight junction formation, as determined by ZO-1 localization. Inducible elimination of integrin α5 abrogates the epithelial-organizing effects of P4G11. In addition, polymerization of fibronectin is required for the effects of P4G11, and addition of polymerized superfibronectin is sufficient to induce tight junction formation and apicobasolateral polarization. In the normal human colon, we show that integrin α5 localizes to the lateral membrane of terminally differentiated colonocytes and that integrin α5 staining may be reduced in colorectal cancer. Thus we propose a novel role for integrin α5β1 in regulating epithelial morphogenesis. The American Society for Cell Biology 2017-05-15 /pmc/articles/PMC5426844/ /pubmed/28356422 http://dx.doi.org/10.1091/mbc.E16-12-0852 Text en © 2017 Starchenko et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Starchenko, Alina
Graves-Deal, Ramona
Yang, Yu-Ping
Li, Cunxi
Zent, Roy
Singh, Bhuminder
Coffey, Robert J.
Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells
title Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells
title_full Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells
title_fullStr Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells
title_full_unstemmed Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells
title_short Clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells
title_sort clustering of integrin α5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426844/
https://www.ncbi.nlm.nih.gov/pubmed/28356422
http://dx.doi.org/10.1091/mbc.E16-12-0852
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