Cleavage of E-cadherin by matrix metalloproteinase-7 promotes cellular proliferation in nontransformed cell lines via activation of RhoA

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. © 2010 conor c. lynch et al.