Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma

Beomseok Son, Sungmin Lee, Hyunwoo Kim, Hyunkoo Kang, Jaewan Jeon, Sunmi Jo, Ki Moon Seong, Su Jae Lee, Hye Sook Youn, Bu Hyun Youn

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)36-49
Number of pages14
JournalOncogene
Volume39
Issue number1
DOIs
StatePublished - 2020 Jan 2

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Fructose-Bisphosphatase
Glioblastoma
Ionizing Radiation
Radiotherapy
Glycolysis
Down-Regulation
Phosphoglycerate Mutase
Emodin
Gluconeogenesis
Therapeutics
Heterografts
Glucose
Enzymes
Neoplasms

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Son, B., Lee, S., Kim, H., Kang, H., Jeon, J., Jo, S., ... Youn, B. H. (2020). Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma. Oncogene, 39(1), 36-49. https://doi.org/10.1038/s41388-019-0974-4
Son, Beomseok ; Lee, Sungmin ; Kim, Hyunwoo ; Kang, Hyunkoo ; Jeon, Jaewan ; Jo, Sunmi ; Seong, Ki Moon ; Lee, Su Jae ; Youn, Hye Sook ; Youn, Bu Hyun. / Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma. In: Oncogene. 2020 ; Vol. 39, No. 1. pp. 36-49.
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Son, B, Lee, S, Kim, H, Kang, H, Jeon, J, Jo, S, Seong, KM, Lee, SJ, Youn, HS & Youn, BH 2020, 'Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma', Oncogene, vol. 39, no. 1, pp. 36-49. https://doi.org/10.1038/s41388-019-0974-4

Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma. / Son, Beomseok; Lee, Sungmin; Kim, Hyunwoo; Kang, Hyunkoo; Jeon, Jaewan; Jo, Sunmi; Seong, Ki Moon; Lee, Su Jae; Youn, Hye Sook; Youn, Bu Hyun.

In: Oncogene, Vol. 39, No. 1, 02.01.2020, p. 36-49.

Research output: Contribution to journalArticle

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T1 - Decreased FBP1 expression rewires metabolic processes affecting aggressiveness of glioblastoma

AU - Son, Beomseok

AU - Lee, Sungmin

AU - Kim, Hyunwoo

AU - Kang, Hyunkoo

AU - Jeon, Jaewan

AU - Jo, Sunmi

AU - Seong, Ki Moon

AU - Lee, Su Jae

AU - Youn, Hye Sook

AU - Youn, Bu Hyun

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N2 - 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.

AB - 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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