Título: Bivalent roles of Vav oncoproteins as tumor promoters and suppressors

Ponente: Dr. Xosé R. Bustelo

Día y hora: Viernes 5  de Octubre a las 12.30

Lugar: SALA DE CONFERENCIAS, EDIFICIO I+D+i, CAMPUS RIO EBRO

Rho GDP/GTP exchange factors (GEFs) are enzymes that promote the activation of Rho GTPases in both normal and cancer cells. Due to this, it is widely assumed that they can represent potential anticancer drug targets. However, we still have very little information about the actual role of these enzymes in human cancer, the therapeutic effectiveness of inhibiting their enzyme activities, and the side effects that such inhibition elicits in healthy tissues. Our group is trying to address these issues using as main tool the three known members of the Vav GEF family, the proteins Vav1, Vav2 and Vav3. To this end, we are utilizing a multifaceted approach based on the use of genetically modified mice, genome wide expression profiling techniques, cross-species transcriptomal comparisons, and patient-derived cell models. In my talk, I will present recent data demonstrating that the endogenous wild type and mutant versions of these proteins play proactive roles in mature T cell leukemia and a variety of epithelial tumors. Furthermore, I will discuss data from our “pharmaco-mimetic” knock-in mice demonstrating that the inhibition of GEFs does have a negative impact on the fitness of tumor cells in vivo. Perhaps more importantly, these studies also have revealed the feasibility of dissociating the positive and negative effects elicited by the inhibition of Vav proteins depending on the level of catalytic silencing achieved at the organismal level.