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Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma

Oncogene volume 39, pages 36–49 (2020)Cite this article

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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.

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Acknowledgements

This work was supported by the Nuclear Safety Research Program through the Korea Foundation Of Nuclear Safety (KoFONS) using the financial resource granted by the Nuclear Safety and Security Commission (NSSC) of the Republic of Korea (No. 1805019). We thank Dr. Akio Soeda (Gifu University) for providing patient-derived X01 GBM cells.

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  1. These authors contributed equally: Beomseok Son, Sungmin Lee

Authors and Affiliations

  1. Department of Integrated Biological Science, Pusan National University, Busan, 46241, Republic of Korea

    Beomseok Son, Sungmin Lee, Hyunwoo Kim, Hyunkoo Kang, Jaewan Jeon & BuHyun Youn

  2. Department of Radiation Oncology, Haeundae Paik Hospital, Inje University School of Medicine, Busan, 48108, Republic of Korea

    Jaewan Jeon & Sunmi Jo

  3. Laboratory of Low Dose Risk Assessment, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul, 01812, Republic of Korea

    Ki Moon Seong

  4. Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, 04763, Republic of Korea

    Su-Jae Lee

  5. Department of Integrative Bioscience and Biotechnology, Sejong University, Seoul, 05006, Republic of Korea

    HyeSook Youn

  6. Department of Biological Sciences, Pusan National University, Busan, 46241, Republic of Korea

    BuHyun Youn

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Son, B., Lee, S., Kim, H. et al. Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma. Oncogene 39, 36–49 (2020). https://doi.org/10.1038/s41388-019-0974-4

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