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

BENZO Y.; DATTILO M.; PRADA J.; HELFENBERGER K.; HERRERA L.; PODEROSO C.; MALOBERTI P.

Mar del Plata, Buenos Aires

Congreso; REUNION CONJUNTA SAIC SAI SAFIS 2018; 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 cell lines. It has been demonstrated that ACSL4 expression promotes tumor aggressiveness by increasing migration, proliferation and invasion. Little is known about transcriptional and post translational regulation of this enzyme in breast cancer cell lines (Maloberti P. Plos One 2010). We have found several transcription factors that could be involved in ACSL4 regulation, among them, Estrogen Related Receptor alpha (ERRα) might be a candidate in the regulation of this enzyme expression. ACSL4 is also regulated by post translational modifications. In hepatocytes, it has been shown that ACSL4 is ubiquitinated and degraded by the proteasome. However, little is known about the role of ubiquitination and protein stability in the differential expression of ACSL4. In this work, MCF-7 and MDA ?MB-231 cells were used as two different models of breast cancer (ER+,PR+,HER2 and triple negative respectively). Our goal was to study the regulation of ACSL4 by transcriptional and post translational mechanisms in breast cancer cell lines.