Abstract 4317: EGLN1/c-Myc induced lymphoid-specific helicase inhibits ferroptosis through lipid metabolic gene expression changes

Abstract

Abstract Ferroptosis has emerged as a new form of non-apoptotic cell death in multiple human diseases. However, the epigenetic mechanisms of ferroptosis remain poorly defined. We demonstrate that Lymphoid-specific helicase (LSH), a DNA methylation modifier, interacts with WDR76 to inhibit ferroptosis by activating lipid metabolism-associated genes, including GLUT1, and ferroptosis related genes SCD1 and FADS2. These effects are dependent on iron and lipid reactive oxygen species. We further show that EGLN1 and c-Myc directly activate LSH expression by inhibiting HIF-1α. Finally, we demonstrate that LSH functions as an oncogene in lung cancer in vitro and in vivo. Therefore, our study elucidates the molecular basis for a c-Myc/EGLN1-mediated induction of LSH expression to inhibit ferroptosis, which can be exploited for the development of therapeutic agents to target ferroptosis in cancer. Note: This abstract was not presented at the meeting. Citation Format: Yongguang Tao, Shuang Liu, Yiqun Jiang. EGLN1/c-Myc induced lymphoid-specific helicase inhibits ferroptosis through lipid metabolic gene expression changes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4317. doi:10.1158/1538-7445.AM2017-4317