Abstract 2369: AMPK regulation of apoptosis through OSBP

Alterations in lipid metabolism have been frequently reported in tumor progression, with impaired PI(4,5)P 2 homeostasis in the plasma membrane implicated in various cancers and metabolic disorders. Oxysterol binding protein (OSBP) and its related proteins (ORPs) constitute a large family of ubiquitously expressed, evolutionarily conserved lipid binding proteins that play critical roles in intracellular lipid trafficking. OSBP and ORPs associate with a wide range of cellular activities, however their functions and regulations are largely unclear. Emerging evidence has supported an essential role of OSBP in cell signaling pathways and cancer development. We recently identified yeast oxysterol binding protein Osh7 as a true substrate of yeast AMPK (Snf1). AMPK9s involvement in cancer has been extensively studied in the past decade, and is an important mediator of cellular energy homeostasis. Despite many downstream targets identified, AMPK is not known to regulate oxysterol binding protein activities. We found that Snf1 may be responsible for the degradation of Osh7 and cells deficient in Osh7 and its homolog Osh6 display higher rates of apoptosis. Understanding the regulation of OSBP by AMPK may aid in better targeting AMPK for cancer treatment and prevention, at the same time provide a better understanding to the roles of OSBP in cancer development. Citation Format: Kai Li Ong, Trever Thurgood, Michael Christensen, Jonny Malmrose, Denise Ng, Julianne Grose. AMPK regulation of apoptosis through OSBP [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 2369.