Role of p120ctn in Cadherin Mediated Suppression of Breast Cancer

摘要

In the previous reporting periods, we showed that cadherin binding is necessary to recruit p12O to cell junctions and that p12O is important to the generation of strong cell-cell adhesion. We have extended these observations to show that p12O acts at the cell surface to control cadherin turnover, thereby directly regulating cadherin levels. p12O knockdown by siRNA expression results in dose-dependant elimination of E-, P-, N-, and VE-cadherins, and complete loss of cell-cell adhesion. p120 family members ARVOF and 8-catenin are functionally redundant. The data reveal the core function of p12O in cadherin complexes, and strongly predict a dose-dependant loss of E-cadherin in tumors that partially or completely downregulate p12O. These data suggest a crucial and largely unrecognized tumor suppressor role for p12O, which will guide further studies aimed at determining whether p12O loss contributes to tumor progression in the breast.