Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival

Molecular Cancer

Research

Anja Pucer¹  Jože Pungerčar¹  Vesna Brglez¹  Toni Petan¹  Gérard Lambeau²  Christine Payré² 

[1] Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia;Institut de Pharmacologie Moléculaire et Cellulaire, CNRS et Université de Nice Sophia Antipolis, UMR 6097, Sophia Antipolis Valbonne, France;

关键词: Secreted phospholipase A;    Breast cancer;    Cell survival;    Apoptosis;    Lipid droplets;    Fatty acid oxidation;    Lipid signaling;    Etomoxir;    Carnitine palmitoyltransferase 1;    AMP-activated protein kinase;   

DOI  :  10.1186/1476-4598-12-111

 received in 2013-07-04, accepted in 2013-09-24,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundAlterations in lipid metabolism are inherent to the metabolic transformations that support tumorigenesis. The relationship between the synthesis, storage and use of lipids and their importance in cancer is poorly understood. The human group X secreted phospholipase A2 (hGX sPLA2) releases fatty acids (FAs) from cell membranes and lipoproteins, but its involvement in the regulation of cellular FA metabolism and cancer is not known.ResultsHere we demonstrate that hGX sPLA2 induces lipid droplet (LD) formation in invasive breast cancer cells, stimulates their proliferation and prevents their death on serum deprivation. The effects of hGX sPLA2 are shown to be dependent on its enzymatic activity, are mimicked by oleic acid and include activation of protein kinase B/Akt, a cell survival signaling kinase. The hGX sPLA2-stimulated LD biogenesis is accompanied by AMP-activated protein kinase (AMPK) activation, up-regulation of FA oxidation enzymes and the LD-coating protein perilipin 2, and suppression of lipogenic gene expression. Prolonged activation of AMPK inhibited hGX sPLA2-induced LD formation, while etomoxir, an inhibitor of FA oxidation, abrogated both LD formation and cell survival. The hGX sPLA2-induced changes in lipid metabolism provide a minimal immediate proliferative advantage during growth under optimal conditions, but they confer to the breast cancer cells a sustained ability to resist apoptosis during nutrient and growth factor limitation.ConclusionOur results identify hGX sPLA2 as a novel modulator of lipid metabolism that promotes breast cancer cell growth and survival by stimulating LD formation and FA oxidation.

【 授权许可】

Unknown   
© Pucer et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.