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Dr. Zent and colleagues article published in Molecular Biology Cell

April 14th 2017

Mol Biol Cell. 2017 Mar 29. pii: mbc.E16-12-0852. doi: 10.1091/mbc.E16-12-0852. [Epub ahead of print]

"Clustering of Integrin alpha 5 at the lateral membrane restores epithelial polarity in invasive colorectal cancer cells"

Starchenko A1, Graves-Deal R2, Yang YP2, Li C2, Zent R2, Singh B2, Coffey RJ3,4.



Apico-basolateral 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 that establishes apico-basolateral 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 3D type-1 collagen reverts the invasive phenotype and restores apico-basolateral 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. Additionally, polymerization of fibronectin is required for the effects of P4G11, and addition of polymerized super-fibronectin is sufficient to induce tight junction formation and apico-basolateral polarization. In 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.

© 2017 by The American Society for Cell Biology

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