UNDERSTANDING THE ROLE OF Vav3 IN MELANOMA

NAHUEL CESATTI LALUCE; MACARENA MAMBERTO; LUCIANO ANSELMINO; FLORENCIA MALIZIA; MAURICIO MENACHO MÁRQUEZ

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

At present, melanoma is the skin cancer type with the poorest prognosis. A deeper understanding at molecular level of this disease may hold the key to improving its treatment.Vav proteins are guanosine nucleotide exchange factors (GEFs) which activate -principally- Rho-Rac GTPases. This family is involved in several processes linked to tumoral and metastasis development. As GEFs, they normally are considered as protumorigenic proteins. Our team is focused on characterizing the role of these proteins in cancer. Previously, we found an unexpectedly antagonistic role between Vav2 and Vav3 in the context of melanoma. Through a bioinformatic approach, we found that Vav3 has the highest expression levels among Vav proteins in normal skin and that expression decreases after UV exposure, while the opposite is observed for Vav2. We previously shown that Vav3 modulates migration and proliferation in melanoma cells. In this report, we demonstrate by annexin V staining and flow cytometry that Vav3 expression triggers apoptosis in vitro in the absence of death stimuli (p=0.05).Considering the GEF role of Vav3 on Rho-Rac, we focused on actin cytoskeleton in mouse melanoma cells after modulating Vav3 expression by transfection techniques. We found that overall cellular architecture is deeply affected by the modulation of Vav3 expression. Indeed, reduced Vav3 levels promote typical migratory actin structures on the membrane. By microarray-based expression assays with these cells, we analyzed transcriptional changes associated to Vav3 expression, noting that this protein modulates the expression of a wide group of genes. An analysis of these differentially expressed genes shed light on biological processes underlying different phenotypes we previously found in vitro and in vivo, as the altered migratory ability of cells associated to Vav3 expression (FDR