Rho GEFs and cancer: linking gene expression and metastatic dissemination.

Guanine nucleotide exchange factors (GEFs) that promote GTP loading onto the guanosine triphosphatases (GTPases) Rho and Rac are prominent players in cancer progression. Recent studies have highlighted the relevance of several GEFs, including the phosphatidylinositol 3,4,5-trisphosphate Rac exchangers P-Rex1 and P-Rex2a, in breast tumorigenesis. New evidence suggests that the exchange factors Vav2 and Vav3 play synergistic roles in breast cancer by sustaining tumor growth, neoangiogenesis, and metastasis. The identification of a Vav-regulated transcriptome and Vav-related genes that control specific steps of metastatic dissemination of breast cancer cells to the lungs highlights the complexities of the signaling networks regulated by Rho/Rac GTPases and may lead to novel therapeutic targets.