Abstract 2419: Lipid droplets promote glioblastoma cell growth through maintaining cholesterol homeostasis mediated by autophagy

Abstract

Abstract Lipid droplets (LDs) have been studied as the major storage site of neutral lipids for decades, especially in the progression of metabolic diseases. Recently, the functions of LDs in cancers have begun to gain significant attention. Here, we provide evidence that LDs promote glioblastoma (GBM) cell growth through autophagy mediated maintenance of cholesterol homeostasis. Our data showed that LDs in tumor tissues from GBM patients are engulfed by autophagic vacuoles and lysosomes. Cellular cholesterol deprivation or removal of plasma membrane cholesterol by methyl-β-cyclodextrin (MβCD) activates autophagy to hydrolyze LDs to support GBM cell survival, whereas inhibition of autophagy blocks transportation of cholesterol to plasma membrane, leading to cell death. Fluorescence imaging reveals direct trafficking of LD-stored cholesterol to the plasma membrane through autophagic liberation. Our data demonstrate that LDs serve as cholesterol reservoir for GBM cell growth, suggesting that targeting LD-autophagy-cholesterol homeostasis metabolic pathway represents a potential means to treat GBM and other malignancies. Citation Format: Feng Geng, Xiang Cheng, Chunming Cheng, Arnab Chakravarti, Deliang Guo. Lipid droplets promote glioblastoma cell growth through maintaining cholesterol homeostasis mediated by autophagy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2419.