title: 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.
authors.affiliation: Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA ; Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Ward
authors.forename: Danny N
authors.initials: DN
authors.lastname: Dhanasekaran
keywords: G protein; Gαi2; LPA; migration; ovarian cancer; p130Cas