G protein signaling in tumor cell growth and metastasis

G protein signaling has been implicated in different aspects cancer growth and progression. Our studies have identified that the G12-family of G proteins that defines the gep family of oncogenes are critically involved in tumor cell proliferation and metastasis. Defining these pathways has shown that the gep protooncogene GNA12 is specifically involved in the proliferation of ovarian cancer cells whereas GNA13 is involved in cancer cell metastasis. Consequently, the silencing of the gep proto-oncogenes potently inhibited tumor growth of ovarian cancer cells in a mouse xenograft model, thus suggesting the dominant role for the gep oncogenes in ovarian cancer growth and progression. In addition we demonstrate a similar role for GNA13 in the invasive migration of pancreatic cancer cells. Furthermore, we demonstrate that an eleven amino acid peptide derived from the gep oncogenes Gα_12/13 can effectively disrupt LPA-stimulated oncogenic pathways. Thus, in addition to unraveling the molecular mechanism underlying cancer progression and metastasis, our results provide evidence that the G protein signaling nodes can be targeted for cancer chemotherapy.

This work was supported by grants from the National Institutes of Health (CA123233, CA 125752, CA 116984).