Epithelial mesenchymal transition and metastasis are closely related.Aberrant activation of the signaling events involved in these inter-related pathways plays a major pathophysiological role in cancer progression and metastasis.Our studies focused on identifying the critical molecule(s) involved in these pathways have identified a distinct roles for the two gep oncogenes namely, G12 and G1s in both tumorigenesis and tumor progression.Our studies to identify the underlying signaling mechanisms have established that Gα12 accelerates cell growth and neoplastic transformation,especially in the case of ovarian cancers, by promoting an autocrine signaling loop involving specific receptor tyrosine kinases.In addition, our results point to a critical role for Gα3 in the invasive migration of cancer cells.Our recent studies have identified that Gα13 plays a critical role in spatio-temporal regulation of Rac-mediated cytoskeletal dynamics by interacting with β-PIX, a Rac/CDC42-specific guanine nucleotide exchange factor.Our results indicate the unique mechanism by which Gα13 differentially regulate Rac-activation as well as inhibition by interacting with β-PIX.Our results also indicate this interaction as a mechanism by which lysophoaphtidic acid, a lipid growth factor that is known to play a role in tumor progression and metastasis, regulate different phases of cancer cell metastasis.In addition to understanding the molecular mechanism underlying tumor cell progression and metastasis, our results provide evidence that the gep oncogenes and their signaling pathways can be targeted for cancer chemotherapy.This work was supported by grants from the National Institutes of Health (CA123233, CA 125752, CA 116984) and World Class University project funded by Ministry of Education, Science and Technology Development, S.Korea [No.R32-2008-000-10098-0].