IN VITRO STUDY OF THE ROLE OF VAV PROTEINS IN MELANOMA

NAHUEL CESATTI LALUCE; MACARENA MAMBERTO; JULIÁN GUERCETTI; LUCIANO ANSELMINO; FLORENCIA MALIZIA; GIRARDINI, JAVIER; MAURICIO MENACHO MÁRQUEZ

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. Vav proteins are guanosine nucleotide exchange factors (GEFs) of the Rho GTPase family. As GEFs, they modulate processes highly associated to the development of cancer and metastasis, mostly through their GTPase regulatory function, but their involvement in melanoma is yet to be elucidated. Previous results of our group demonstrated by in vitro studies a role for Vav2 in melanoma cells proliferation and migration. To further explore the role of this protein in melanoma development, we performed in vivo experiments. Using shRNA techniques and transfection with expression vectors, we modulated Vav2 expression or activity in B16-F0 melanoma cell lines. These cells (2x105 cells/100 μL) were subcutaneously injected in the right flank of 8 weeks-old C57Bl6 female mice (n= 7-9/group). Tumor volume was measured with a calliper biweekly during 3 weeks. At the end of the experiment mice were sacrificed to collect tumor samples and lungs. Growth kinetics indicated that tumors with reduced expression of Vav2 grow slowly than the control (doubling time 1.71 ± 0.08 versus 1.53 ± 0.11; p