Abstract 3598: Phosphoglycerate mutase 1 inhibitor causes metabolic disadvantages in glioblastoma by rescue of FBP1 repression

Abstract

Abstract Radiotherapy is a primary treatment for patients with glioblastoma (GBM). Despite high therapeutic efficacy, the tumor cells that survive after radiotherapy may cause side effects. In this study, we found that fructose 1,6-bisphosphatase 1 (FBP1) which is a rate-limiting enzyme in gluconeogenesis was downregulated upon treatment with ionizing radiation (IR). IR-induced infiltrating GBM has overexpressed Ets1 which was suggested to be a transcriptional repressor of FBP1. Besides, glucose uptake and extracellular acidification rates were increased upon FBP1 downregulation, which indicated an elevated glycolysis level. We found that emodin, an inhibitor of phosphoglycerate mutase 1 derived from natural substances, significantly suppressed the glycolysis rate and the IR-induced GBM aggressiveness in the in vivo orthotopic xenograft mouse models. We propose that the downregulation of FBP1 level reprogrammed the metabolic state of GBM, and thus, FBP1 is a promising therapeutic target regulating GBM metabolism following radiotherapy. Note: This abstract was not presented at the meeting. Citation Format: Sungmin Lee, Hyunwoo Kim, Hyunkoo Kang, BuHyun Youn. Phosphoglycerate mutase 1 inhibitor causes metabolic disadvantages in glioblastoma by rescue of FBP1 repression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3598.