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Suppression of mitochondrial ROS by prohibitin drives glioblastoma progression and therapeutic resistance

Author

Listed:
  • Haohao Huang

    (National Center of Biomedical Analysis
    Nanhu Laboratory, Jiaxing
    General Hospital of Central Theater Command of Chinese People’s Liberation Army)

  • Songyang Zhang

    (National Center of Biomedical Analysis)

  • Yuanyuan Li

    (National Center of Biomedical Analysis)

  • Zhaodan Liu

    (National Center of Biomedical Analysis)

  • Lanjuan Mi

    (National Center of Biomedical Analysis)

  • Yan Cai

    (National Center of Biomedical Analysis)

  • Xinzheng Wang

    (National Center of Biomedical Analysis)

  • Lishu Chen

    (National Center of Biomedical Analysis)

  • Haowen Ran

    (National Center of Biomedical Analysis)

  • Dake Xiao

    (National Center of Biomedical Analysis)

  • Fangye Li

    (First Medical Center of PLA General Hospital)

  • Jiaqi Wu

    (National Center of Biomedical Analysis)

  • Tingting Li

    (National Center of Biomedical Analysis)

  • Qiuying Han

    (National Center of Biomedical Analysis)

  • Liang Chen

    (National Center of Biomedical Analysis)

  • Xin Pan

    (National Center of Biomedical Analysis)

  • Huiyan Li

    (National Center of Biomedical Analysis)

  • Tao Li

    (National Center of Biomedical Analysis)

  • Kun He

    (National Center of Biomedical Analysis)

  • Ailing Li

    (National Center of Biomedical Analysis
    The First Hospital of Jilin University)

  • Xuemin Zhang

    (National Center of Biomedical Analysis
    The First Hospital of Jilin University
    National Center of Biomedical Analysis)

  • Tao Zhou

    (National Center of Biomedical Analysis
    Nanhu Laboratory, Jiaxing)

  • Qing Xia

    (National Center of Biomedical Analysis)

  • Jianghong Man

    (National Center of Biomedical Analysis
    Nanhu Laboratory, Jiaxing)

Abstract

Low levels of reactive oxygen species (ROS) are crucial for maintaining cancer stem cells (CSCs) and their ability to resist therapy, but the ROS regulatory mechanisms in CSCs remains to be explored. Here, we discover that prohibitin (PHB) specifically regulates mitochondrial ROS production in glioma stem-like cells (GSCs) and facilitates GSC radiotherapeutic resistance. We find that PHB is upregulated in GSCs and is associated with malignant gliomas progression and poor prognosis. PHB binds to peroxiredoxin3 (PRDX3), a mitochondrion-specific peroxidase, and stabilizes PRDX3 protein through the ubiquitin-proteasome pathway. Knockout of PHB dramatically elevates ROS levels, thereby inhibiting GSC self-renewal. Importantly, deletion or pharmacological inhibition of PHB potently slows tumor growth and sensitizes tumors to radiotherapy, thus providing significant survival benefits in GSC-derived orthotopic tumors and glioblastoma patient-derived xenografts. These results reveal a selective role of PHB in mitochondrial ROS regulation in GSCs and suggest that targeting PHB improves radiotherapeutic efficacy in glioblastoma.

Suggested Citation

  • Haohao Huang & Songyang Zhang & Yuanyuan Li & Zhaodan Liu & Lanjuan Mi & Yan Cai & Xinzheng Wang & Lishu Chen & Haowen Ran & Dake Xiao & Fangye Li & Jiaqi Wu & Tingting Li & Qiuying Han & Liang Chen &, 2021. "Suppression of mitochondrial ROS by prohibitin drives glioblastoma progression and therapeutic resistance," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24108-6
    DOI: 10.1038/s41467-021-24108-6
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