LPA Stimulates the Phosphorylation of p130Cas via Gαi2 in Ovarian Cancer Cells

Abstract

Ovarian cancer is the most deadly gynecological cancer, with previous studies implicating lysophosphatidic acid (LPA) in the progression of approximately 90% of all ovarian cancers. LPA potently stimulates the tyrosine phosphorylation of p130Cas, a scaffolding protein, which, upon phosphorylation, recruits an array of signaling molecules to promote tumor cell migration. Our work presented here identifies Gαi2 as the major G protein involved in tyrosine phosphorylation of p130Cas in a panel of ovarian cancer cells consisting of HeyA8, SKOV3, and OVCA429. Our results also indicate that the G12 family of G proteins that are also involved in LPA-mediated migration inhibits tyrosine phosphorylation of p130Cas. Using p130Cas siRNA, we demonstrate that p130Cas is a necessary downstream component of LPA Gαi2-induced migration and collagen-1 invasion of ovarian cancer cells. Considering the fact that LPA stimulates invasive migration through the coordination of multiple downstream signaling pathways, our current study identifies a separate unique signaling node involving p130Cas and Gαi2 in mediating LPA-mediated invasive migration of ovarian cancer cells. © The Author(s) 2013.