Regulator of G-protein signaling 5 blunts cellular viability mediated by a stabilized lysophosphatidic acid analogue (2S-OMPT) in the presence of chemotherapy in an ovarian cancer cell model of chemoresistance

Abstract

Every year approximately 22,000 women in the United states are diagnosed with ovarian cancer. Ovarian cancer is the fifth leading cause of cancer related death among women in the United States. Lysophasphatidic acid (LPA) enhances growth, survival, viability and proliferation in numerous tumor models. Thus, the receptors for LPA are also implicated in oncogenic signaling and represent a group of “druggable” therapeutic targets in cancer. Regulator of G protein signaling 5 (RGS5) is a GTPase activating protein (GAP) that deactivates the G alpha subunits of heterotrimeric G proteins, turning off G protein- coupled receptor (GPCR) signaling. In our previous studies examining computational bioinformatics, we demonstrated that reduced RGS5 expression develops with the occurrence of drug resistance in ovarian cancer cell lines. The purpose of our study was to investigate whether LPA receptors are also involved in mediating viability as a result of reduced GPCR signaling due to enhanced RGS5 protein expression in this chemoresistance model.