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MYG1 drives glycolysis and colorectal cancer development through nuclear-mitochondrial collaboration

Author

Listed:
  • Jianxiong Chen

    (Southern Medical University
    Southern Medical University)

  • Shiyu Duan

    (Southern Medical University
    Southern Medical University)

  • Yulu Wang

    (Southern Medical University
    Southern Medical University)

  • Yuping Ling

    (Southern Medical University
    Southern Medical University)

  • Xiaotao Hou

    (Southern Medical University
    Southern Medical University)

  • Sijing Zhang

    (Southern Medical University
    Southern Medical University)

  • Xunhua Liu

    (Southern Medical University
    Southern Medical University)

  • Xiaoli Long

    (Southern Medical University
    Southern Medical University)

  • Jiawen Lan

    (Southern Medical University
    Southern Medical University)

  • Miao Zhou

    (Southern Medical University)

  • Huimeng Xu

    (Southern Medical University
    Southern Medical University)

  • Haoxuan Zheng

    (Southern Medical University)

  • Jun Zhou

    (Southern Medical University
    Southern Medical University)

Abstract

Metabolic remodeling is a strategy for tumor survival under stress. However, the molecular mechanisms during the metabolic remodeling of colorectal cancer (CRC) remain unclear. Melanocyte proliferating gene 1 (MYG1) is a 3′−5′ RNA exonuclease and plays a key role in mitochondrial functions. Here, we uncover that MYG1 expression is upregulated in CRC progression and highly expressed MYG1 promotes glycolysis and CRC progression independent of its exonuclease activity. Mechanistically, nuclear MYG1 recruits HSP90/GSK3β complex to promote PKM2 phosphorylation, increasing its stability. PKM2 transcriptionally activates MYC and promotes MYC-medicated glycolysis. Conversely, c-Myc also transcriptionally upregulates MYG1, driving the progression of CRC. Meanwhile, mitochondrial MYG1 on the one hand inhibits oxidative phosphorylation (OXPHOS), and on the other hand blocks the release of Cyt c from mitochondria and inhibits cell apoptosis. Clinically, patients with KRAS mutation show high expression of MYG1, indicating a high level of glycolysis and a poor prognosis. Targeting MYG1 may disturb metabolic balance of CRC and serve as a potential target for the diagnosis and treatment of CRC.

Suggested Citation

  • Jianxiong Chen & Shiyu Duan & Yulu Wang & Yuping Ling & Xiaotao Hou & Sijing Zhang & Xunhua Liu & Xiaoli Long & Jiawen Lan & Miao Zhou & Huimeng Xu & Haoxuan Zheng & Jun Zhou, 2024. "MYG1 drives glycolysis and colorectal cancer development through nuclear-mitochondrial collaboration," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49221-0
    DOI: 10.1038/s41467-024-49221-0
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    References listed on IDEAS

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    1. Weiwei Yang & Yan Xia & Haitao Ji & Yanhua Zheng & Ji Liang & Wenhua Huang & Xiang Gao & Kenneth Aldape & Zhimin Lu, 2011. "Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation," Nature, Nature, vol. 480(7375), pages 118-122, December.
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