Possible association of low glycolytic phenotype with BRAFV600R mutation in melanoma cells

ARBE, MF; LODILLISNKY, C; KRASNAPOLSKY, M; GLIKIN, GC.; FINOCCHIARO, LM.E; VILLAVERDE, MS

Congreso; LXII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2017

Abstract: Altered metabolism of cancer cells favors not only proliferation but also therapy resistance. BRAF mutation represent the most prevalent alteration in melanoma patients being V600E mutation more frequent than V600R. Sensitivity to BRAF inhibitors seems to be related to glycolysis dependence. The aim of the present work was to characterize the metabolic phenotype of six BRAF mutated human melanoma cells lines, five V600E subtype (hM1, hM2, hM9, hM10 and A375) and one V600R (hM4). We studied glucose consumption, lactate production, LDH and G6PDH activities (commercial kits), GLUT-1 (WB) and extracellular pH. Interestingly, we found that hM4 cell line presented not only lower glucose consumption and GLUT-1 expression, but also lower LDH and lactate production in parallel with significant higher pH than the other assayed melanoma cells lines. Our data suggest that V600R mutation drives melanoma cells to a lower glycolytic phenotype than V600E mutation.