Plakoglobin Reduces the in vitro Growth, Migration and Invasion of Ovarian Cancer Cells Expressing N-Cadherin and Mutant p53

Aberrant expression of cadherins and catenins plays pivotal roles in ovarian cancer development and progression. Plakoglobin (PG, gamma-catenin) is a paralog of beta-catenin with dual adhesive and signaling functions. While beta-catenin has known oncogenic function, PG generally acts as a tumor/metastasis suppressor. We recently showed that PG interacted with p53 and that its growth/metastasis inhibitory function may be mediated by this interaction. Very little is known about the role of PG in ovarian cancer. Here, we investigated the in vitro tumor/metastasis suppressor effects of PG in ovarian cancer cell lines with mutant p53 expression and different cadherin profiles. We showed that the N-cadherin expressing and E-cadherin and PG deficient ES-2 cells were highly migratory and invasive, whereas OV-90 cells that express E-cadherin, PG and very little/no N-cadherin were not. Exogenous expression of PG or E-cadherin or N-cadherin knockdown in ES-2 cells (ES-2-E-cad, ES-2-PG and ES-2-shN-cad) significantly reduced their migration and invasion. Also, PG expression or N-cadherin knockdown significantly decreased ES-2 cells growth. Furthermore, PG interacted with both cadherins and with wild type and mutant p53 in normal ovarian and ES-2-PG cell lines, respectively.