Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma

Abstract

Radiotherapy is a standard treatment option for patients with glioblastoma (GBM). Although it has high therapeutic efficacy, some proportion of the tumor cells that survive after radiotherapy may cause side effects. In this study, we found that fructose 1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, was downregulated upon treatment with ionizing radiation (IR). Ets1, which was found to be overexpressed in IR-induced infiltrating GBM, was suggested to be a transcriptional repressor of FBP1. Furthermore, 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 IR-induced GBM migration in in vivo orthotopic xenograft mouse models. We propose that the reduced FBP1 level reprogrammed the metabolic state of GBM cells, and thus, FBP1 is a potential therapeutic target regulating GBM metabolism following radiotherapy.