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ATF4-dependent fructolysis fuels growth of glioblastoma multiforme

Author

Listed:
  • Chao Chen

    (Chinese Academy of Sciences)

  • Zhenxing Zhang

    (Chinese Academy of Sciences)

  • Caiyun Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Bin Wang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Ping Liu

    (Chinese Academy of Sciences)

  • Shu Fang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Fan Yang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yongping You

    (The First Affiliated Hospital of Nanjing Medical University
    Nanjing Medical University)

  • Xinjian Li

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

Abstract

Excessive consumption of fructose in the Western diet contributes to cancer development. However, it is still unclear how cancer cells coordinate glucose and fructose metabolism during tumor malignant progression. We demonstrate here that glioblastoma multiforme (GBM) cells switch their energy supply from glycolysis to fructolysis in response to glucose deprivation. Mechanistically, glucose deprivation induces expression of two essential fructolytic proteins GLUT5 and ALDOB through selectively activating translation of activating transcription factor 4 (ATF4). Functionally, genetic or pharmacological disruption of ATF4-dependent fructolysis significantly inhibits growth and colony formation of GBM cells in vitro and GBM growth in vivo. In addition, ATF4, GLUT5, and ALDOB levels positively correlate with each other in GBM specimens and are poor prognostic indicators in GBM patients. This work highlights ATF4-dependent fructolysis as a metabolic feature and a potential therapeutic target for GBM.

Suggested Citation

  • Chao Chen & Zhenxing Zhang & Caiyun Liu & Bin Wang & Ping Liu & Shu Fang & Fan Yang & Yongping You & Xinjian Li, 2022. "ATF4-dependent fructolysis fuels growth of glioblastoma multiforme," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33859-9
    DOI: 10.1038/s41467-022-33859-9
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    References listed on IDEAS

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    1. Zhenxing Zhang & Xin Li & Fan Yang & Chao Chen & Ping Liu & Yi Ren & Pengkai Sun & Zixiong Wang & Yongping You & Yi-Xin Zeng & Xinjian Li, 2021. "DHHC9-mediated GLUT1 S-palmitoylation promotes glioblastoma glycolysis and tumorigenesis," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Andrew V. Anzalone & Peyton B. Randolph & Jessie R. Davis & Alexander A. Sousa & Luke W. Koblan & Jonathan M. Levy & Peter J. Chen & Christopher Wilson & Gregory A. Newby & Aditya Raguram & David R. L, 2019. "Search-and-replace genome editing without double-strand breaks or donor DNA," Nature, Nature, vol. 576(7785), pages 149-157, December.
    Full references (including those not matched with items on IDEAS)

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