Abstract 3791: MAPK p38 is the link between autophagy and lipid metabolism in colorectal cancer cells

Abstract

Abstract Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Recent progress has demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles, notably in cancer. We have showed previously, that the p38 pathway was involved in Irinotecan sensitivity of colon cancer cells p53WT. p38 being involved in the induction of autophagy we wanted to determine its role in the processes of autophagy in presence and in absence of p53 in colorectal cancer cells. Our results show that the overexpression of the constitutively active p38alpha isoform in HCT116 p53KO cells leads to a massive autophagy, accompanied with a block in G2 / M. The induction of autophagy in this context doesn't leads to the cellular death but rather to survival. The autophagy induction by p38 overexpression in HCT116 was weaker, indicating that the lack of p53 increase p38 role in autophagy induction. Furthermore, we have shown that autophagy induced by p38 comes along with an increase of the lipid metabolism by activating a key enzyme of the synthesis of fatty acids. We demonstrate here, that the role of p38 in the induction of autophagy depends on the presence of p53 and that p38 would be the link between the increase of the lipid metabolism and the induction of autophagy that lead to survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3791. doi:10.1158/1538-7445.AM2011-3791