Regulation of Acyl-CoA synthetase 4 (ACSL4) expression by transcriptional and post translational mechanisms in breast cancer cells

BENZO YANINA; DATTILO MELINA; PRADA JESICA G.; HELFENBERGER KATIA; HERRERA LUCIA; PODEROSO CECILIA; MALOBERTI PAULA

Mar del Plata

Congreso; LXIII Reunión anual de la Sociedad Argentina de Investigación Clínica; 2018

Acyl-CoA synthetase 4 (ACSL4) is an enzyme that catalyzes acyl-CoA synthesis from long chain fatty acid, being arachidonic acid its preferred substrate. ACSL4 levels correlate with aggressive phenotype in breast cancer. Its expression promotes tumor aggressiveness by increasing migration, proliferation and invasion. The aim of this work is to describe transcriptional and post traductional mechanisms that could regulate ACSL4 expression in breast cancer cell lines. We demonstrated by ChIP and by the use of a specific inhibitor that Estrogen-related receptor alpha is involved in ACSL4 transcriptional regulation. We studied the participation of proteosomal degradation. ACSL4 protein stability was tested on MCF-7 breast cancer cells with cycloheximide (CHX) treatment. Immunoblot showed a time-dependent decrease in ACSL4 levels after CHX treatment, significant at 2h of CHX (***p