P120ctn and P-cadherin but not E-cadherin regulate cell motility and invasion of DU145 prostate cancer cells

Abstract

Background: Adherens junctions consist of transmembrane cadherins, which interact intracellularly with p120ctn, ß-catenin and a-catenin. p120ctn is known to regulate cell-cell adhesion by increasing cadherin stability, but the effects of other adherens junction components on cell-cell adhesion have not been compared with that of p120ctn. Methodology/Principal Findings: We show that depletion of p120ctn by small interfering RNA (siRNA) in DU145 prostate cancer and MCF10A breast epithelial cells reduces the expression levels of the adherens junction proteins, E-cadherin, Pcadherin, ß-catenin and a-catenin, and induces loss of cell-cell adhesion. p120ctn-depleted cells also have increased migration speed and invasion, which correlates with increased Rap1 but not Rac1 or RhoA activity. Downregulation of Pcadherin, b-catenin and a-catenin but not E-cadherin induces a loss of cell-cell adhesion, increased migration and enhanced invasion similar to p120ctn depletion. However, only p120ctn depletion leads to a decrease in the levels of other adherens junction proteins. Conclusions/Significance: Our data indicate that P-cadherin but not E-cadherin is important for maintaining adherens junctions in DU145 and MCF10A cells, and that depletion of any of the cadherin-associated proteins, 120ctn, ß-catenin or a-catenin, is sufficient to disrupt adherens junctions in DU145 cells and increase migration and cancer cell invasion. © 2010 Kuemper, Ridley.