STUDY OF THE ROLE OF MODULATORS OF SMALL GTPASES IN MELANOM

MAURICIO MENACHO MÁRQUEZ

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

Melanoma is the most dangerous form of skin cancer, accounting for the third highest number of lives lost across all cancers. Since the incidence of melanoma is steadily increasing in the population, finding prognostic and therapeutic targets appears a crucial task in cancer. Vav proteins are guanosine nucleotide exchange factors (GEFs) of the Rho GTPase family whose involvement in melanoma is yet to be elucidated. As GEFs, Vav proteins are capable of regulating processes associated to cytoskeleton rearrangement, mostly through their regulatory function on RhoA and Rac1 GTPases. In this way they manage to modulate cellular migratory capacities and other processes highly associated to the development of cancer and metastasis. In our work we explored the role of Vav proteins in events associated to aggressiveness in melanoma. By modulating theexpression or activity levels of these GEFs we were able to observe that Vav proteins play important roles modulating proliferation, apoptosis, cell morphology and migratory behaviour. Also, members of this family are critical to maintain epithelial traits in melanoma cells. All these events were controlled both in GTPases dependent and independent manners. Interestingly, different members of this GEF family, although close related, play opposite roles controlling melanoma proliferation. Altogether our data indicate a critical role for Vav proteins in development of melanoma and highlight that the elucidation of the role of these proteins in the generation of tumors, their growth and subsequent invasion of nearby tissues, could provide new therapeutic alternatives that contribute to an improvement in current therapies against the main tumor types.