REGULATION OF ACYL-COA SYNTHETASE 4 (ACSL4) EXPRESSION BY TRANSCRIPTIONAL AND POST TRANSCRIPTIONAL MECHANISMS IN BREAST CANCER CELLS

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

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 acylCoA 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< 0,001). To analyse a possible mechanism in ACSL4 ubiquitination, we tested Parkin, that is an E3 ubiquitin ligase involved in cellular aggressiveness in breast tumors. Parkin displays particularly lower expression in MDA-MB-231 than in MCF-7 cells. We performed co-immunoprecipitation experiments in HEK293 cells and observed that Parkin interacts specifically with ACSL4. These results support the role of proteosome degradation in the regulation of ACSL4 levels and suggest that Parkin could be involved in ACSL4 degradation in breast cancer cells.