Abstract LB-84: Mutant p53 enhances the metastatic potential of ovarian cancer cells

Abstract

Abstract Missense-mutations of TP53 resulting in accumulation of mutant proteins are very frequent in human cancer including ovarian cancer. Aggressive ovarian cancer is characterized by a peritoneal metastasis which involves the adhesion, migration, and invasion of tumor cells to the peritoneal cavity. In the present study, we investigated the effect of p53 GOF mutation (p53R248) on the metastatic potential of human ovarian cancer cells. We found that forced overexpression of p53R248 significantly increased adhesion to mesothelial cell Met5A, migration, and invasion in p53-null SKOV-3 cells. Conversely, knockdown of mutant p53 using siRNA significantly compromised p53R248-induced cell adhesion, migration, and invasion. Microarray analysis revealed that several metastasis-related genes including integrins and S1PR1(Sphingosine-1-phosphate receptor 1), and certain signaling pathway including PI3K/AKT were markedly up-regulated in p53R248 transfectant SKOV-3R248 cells. Inhibition of PI3K/Akt signaling using specific inhibitor significantly attenuated p53R248-mediated mesothelial cell adhesion, migration, and invasion. These finding show for the first time that mutant p53R248 may exert gain-of-function activity to regulate metastasis-related gene expression and the PI3K/Akt singling pathway in ovarian cancer. Citation Format: Ji-Hye Ahn, Jong-Gyu Lee, Jung-Hye Choi. Mutant p53 enhances the metastatic potential of ovarian cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-84. doi:10.1158/1538-7445.AM2014-LB-84