Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA. (10th May 2010)

• Record Type: Journal Article
• Authors: Lynch, Conor C.; Vargo-Gogola, Tracy; Matrisian, Lynn M.; Fingleton, Barbara
• Other Names: Al Moustafa Ala-Eddin Academic Editor.
• Is Part Of: Journal of oncology. Volume 2010(2010)
• Publication Date: 2010-05-10
• Subjects: Oncology -- Research -- Periodicals; Tumors -- Periodicals; Neoplasms; Oncology -- Research; Tumors; Periodicals; Periodicals; 616.994
• DOI: 10.1155/2010/530745
• Languages: English
• ISSNs: 1687-8450

Abstract

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.