ACYL-COA SYNTHETASE 4 LEVELS ARE DEPENDENT ON PROTEASOME ACTIVITY AND MODULATE MITOCHONDRIAL METABOLISM REGULATORY PROTEINS EXPRESSION IN BREAST CANCER CELLS.

BENZO, YANINA; DATTILO, MELINA A.; HELFENBERGER, KATIA E.; HERRERA, LUCÍA; PODEROSO, CECILIA; MALOBERTI, PAULA M.

CABA

Congreso; Reunión conjunta de sociedades de Biociencias, 2017; 2017

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 is overexpressed in triple negative breast cancer cells correlating with tumor aggressiveness. We demonstrated that ACSL4 expression is regulated by transcriptional mechanisms in breast cancer cells. But other mechanisms involved in regulating ACSL4 levels might be taken place. It is known that in cancers exists a strong mitochondrial metabolism deregulation. Computational data showed that ACSL4 is a possible candidate for modulating mitochondrial master regulatory genes. Then, our goal is to study stability of ACSL4 by post translational mechanisms and tostudy the role of ACSL4 in the regulation of mitochondrial function. ACSL4 stability was tested on MDA-MB-231 breast cancer cell line with cycloheximide (CHX) treatment. Immunoblot showed a time-dependent decrease in ACSL4 levels after CHX treatment, significant at 4h of CHX (without vs. with CHX 4h: 1 vs 0.5, relativized to control *p