Abstract 897: Lipid metabolism is involved in mitotic slippage-induced SASP upon treatment with anti-mitotic drugs

Abstract

Abstract Aberrant lipid accumulation is a hallmark of cancer. However, there is little known regarding mechanisms linking lipid metabolism to chemotherapy-induced cell fates. Here, we describe lipid accumulation in cells following antimitotic drug-treatment. Cells arrested in mitosis, as well as cells that escaped mitotic arrest and underwent mitotic slippage, showed elevated cytoplasmic lipid droplets. Interestingly, we found that TOFA, an inhibitor that targets acetyl-CoA carboxylase (ACC) and blocks lipid accumulation enhanced survival of antimitotic-treated cells. Our work previously revealed that cells that survive slippage become senescent and confer pro-tumourigenic effects through non-cell-autonomous effects. Modulating lipid biosynthesis in cells post-slippage by TOFA amplified their inflammatory secretion profiles and accelerated development of tumourigenic behavior. In contrast to TOFA, inhibition of lipid accumulation by C75, a drug targeting fatty acid synthase, significantly reduced the production of pro-tumourigenic factors. This suggests that discrete lipid biosynthesis pathways could contribute differentially to the regulation of pro-tumourigenic inflammation. Note: This abstract was not presented at the meeting. Citation Format: Karen C. Crasta, Alex Wong, Bryan Lim. Lipid metabolism is involved in mitotic slippage-induced SASP upon treatment with anti-mitotic drugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 897.