Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoAReport as inadecuate




Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA - Download this document for free, or read online. Document in PDF available to download.

Journal of OncologyVolume 2010 2010, Article ID 530745, 11 pages

Research Article

Department of Cancer Biology, Vanderbilt University School of Medicine, 734 PRB 2220 Pierce Ave, Nashville, TN 37232, USA

Department of Orthopaedics and Rehabilitation, Vanderbilt University School of Medicine, Nashville, TN 37232, USA

Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, South Bend, IN 46617, USA

Received 15 February 2010; Accepted 1 April 2010

Academic Editor: Ala-Eddin Al Moustafa

Copyright © 2010 Conor C. Lynch et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Perturbations in cell-cell contact machinery occur frequently in epithelial cancers and result in increased cancer cell migration and invasion. Previously, we demonstrated that MMP-7, a protease implicated in mammary and intestinal tumor growth, can process the adherens junction component E-cadherin. This observation leads us to test whether MMP-7 processing of E-cadherin could directly impact cell proliferation in nontransformed epithelial cell lines MDCK and C57MG. Our goal was to investigate the possibility that MMP-7 produced by cancer cells may have effects on adjacent normal epithelium. Here, we show that MMP-7 processing of E-cadherin mediates, 1 loss of cell-cell contact, 2 increased cell migration, 3 a loss of epithelial cell polarization and 4 increased cell proliferation via RhoA activation. These data demonstrate that MMP-7 promotes epithelial cell proliferation via the processing of E-cadherin and provide insights into the molecular mechanisms that govern epithelial cell growth.





Author: Conor C. Lynch, Tracy Vargo-Gogola, Lynn M. Matrisian, and Barbara Fingleton

Source: https://www.hindawi.com/



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