CHARACTERIZING A TUMOR SUPPRESSOR ROLE FOR Vav3 IN MELANOMA

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

Congreso; Reunión Conjunta SAIC. SAI. AAFE. NANOMED-AR; 2021

Melanoma is the most deadly form of skin cancer, with globally increasing prevalence and mortality. A better understanding of this pathology at molecular level is a key challenge to improve diagnosticand therapy.Vav proteins are Rho GTPases guanosine nucleotide exchange factors (GEFs). They modulate processes associated to tumor development and metastasis. As GEFS, these proteins were classicallyconsidered as protumoral.We previously characterized the role of Vav2 in melanoma. Now wedescribe that Vav3 and Vav2 display antagonistic roles in this tumortype, contrary to what is described in other cancer types (includingnon-melanoma skin cancers). Through bioinformatic approaches wefound that Vav3 expression varies significantly between healthy skinand melanoma (P≤0.01) while this GEF acts like a double agent inother tumor types.We modulated Vav3 expression in B16-F0 cells. By MTT assayswe observed that Vav3 expression affects proliferation (P≤0.001).We also found Vav3 levels affect both cell morphology and migration capacity; decreased Vav3 promotes a star shape associatedto greater migratory capacity by wound healing assays (P≤0.001),while increased expression induces elongated shape and poor migration (P≤0.001). Indeed, increased expression of Vav3 promotesapoptosis by starvation.By in vivo assays with 8-weeks old C57BL/6 female mice (n=6/group) subcutaneously injected, we demonstrated that Vav3 downmodulation increases tumor growth while high Vav3 levels drastically impairs tumor kinetics.Altogether our data suggest a new tumor suppressor role for Vav3in melanoma