Abstract 1457: SCAP/SREBP-1 regulates lipid metabolism reprogramming in cancer cell

Warburg initial observation shows tumorigenesis is associated with an increased glucose consumption. Recently, accumulating evidence show that lipid metabolism is reprogrammed in cancers. Elevated lipogenesis which contributes to the development of malignant phenotypes is known to meet requirements for cancer cell rapid growth. However, how they interact to promote cancer growth remain unclear. Through biochemistry and molecular biology assays, we find that EGFR signaling, by increasing glucose uptake, promotes N-glycosylation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and consequent activation of SREBP-1, an ER-bound transcription factor with central roles in lipid metabolism. N-glycosylation promotes SCAP stabilization and dissociates from Insig-1, allowing movement of SCAP/SREBP to the Golgi and consequent SREBP activation. Blocking SCAP N-glycosylation ameliorates EGFRvIII-driven glioblastoma growth in xenograft mouse model. These results show glucose consumption and lipogenesis are linked as reciprocal metabolic cross-talk in tumorigenesis, and targeting SCAP and its N-glycosylation may provide a promising means of more effective cancer therapy. Citation Format: chunming cheng, feng geng, xiang cheng, arnab chakravarti, deliang guo. SCAP/SREBP-1 regulates lipid metabolism reprogramming in cancer cell [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 1457.