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Tumour-associated mutant p53 drives the Warburg effect

Author

Listed:
  • Cen Zhang

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey)

  • Juan Liu

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey)

  • Yingjian Liang

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
    Laboratory of Hepatosplenic Surgery, First Affiliated Hospital of Harbin Medical University)

  • Rui Wu

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey)

  • Yuhan Zhao

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
    Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey)

  • Xuehui Hong

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
    Laboratory of Hepatosplenic Surgery, First Affiliated Hospital of Harbin Medical University)

  • Meihua Lin

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey)

  • Haiyang Yu

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
    Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey)

  • Lianxin Liu

    (Laboratory of Hepatosplenic Surgery, First Affiliated Hospital of Harbin Medical University)

  • Arnold J. Levine

    (The Institute for Advanced Study)

  • Wenwei Hu

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey
    Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey)

  • Zhaohui Feng

    (Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey)

Abstract

Tumour cells primarily utilize aerobic glycolysis for energy production, a phenomenon known as the Warburg effect. Its mechanism is not well understood. The tumour suppressor gene p53 is frequently mutated in tumours. Many tumour-associated mutant p53 (mutp53) proteins not only lose tumour suppressive function but also gain new oncogenic functions that are independent of wild-type p53, defined as mutp53 gain of function (GOF). Here we show that tumour-associated mutp53 stimulates the Warburg effect in cultured cells and mutp53 knockin mice as a new mutp53 GOF. Mutp53 stimulates the Warburg effect through promoting GLUT1 translocation to the plasma membrane, which is mediated by activated RhoA and its downstream effector ROCK. Inhibition of RhoA/ROCK/GLUT1 signalling largely abolishes mutp53 GOF in stimulating the Warburg effect. Furthermore, inhibition of glycolysis in tumour cells greatly compromises mutp53 GOF in promoting tumorigenesis. Thus, our results reveal a new mutp53 GOF and a mechanism for controlling the Warburg effect.

Suggested Citation

  • Cen Zhang & Juan Liu & Yingjian Liang & Rui Wu & Yuhan Zhao & Xuehui Hong & Meihua Lin & Haiyang Yu & Lianxin Liu & Arnold J. Levine & Wenwei Hu & Zhaohui Feng, 2013. "Tumour-associated mutant p53 drives the Warburg effect," Nature Communications, Nature, vol. 4(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3935
    DOI: 10.1038/ncomms3935
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    Cited by:

    1. Juan Liu & Yiyun Shen & Jie Liu & Dandan Xu & Chun-Yuan Chang & Jianming Wang & Jason Zhou & Bruce G. Haffty & Lanjing Zhang & Jill Bargonetti & Subhajyoti De & Wenwei Hu & Zhaohui Feng, 2025. "Lipogenic enzyme FASN promotes mutant p53 accumulation and gain-of-function through palmitoylation," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    2. An Xu & Mo Liu & Mo-Fan Huang & Yang Zhang & Ruifeng Hu & Julian A. Gingold & Ying Liu & Dandan Zhu & Chian-Shiu Chien & Wei-Chen Wang & Zian Liao & Fei Yuan & Chih-Wei Hsu & Jian Tu & Yao Yu & Taylor, 2023. "Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Camilla Tombari & Alessandro Zannini & Rebecca Bertolio & Silvia Pedretti & Matteo Audano & Luca Triboli & Valeria Cancila & Davide Vacca & Manuel Caputo & Sara Donzelli & Ilenia Segatto & Simone Vodr, 2023. "Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    4. Derek Wong & Maha Tageldein & Ping Luo & Erik Ensminger & Jeffrey Bruce & Leslie Oldfield & Haifan Gong & Nicholas William Fischer & Brianne Laverty & Vallijah Subasri & Scott Davidson & Reem Khan & A, 2024. "Cell-free DNA from germline TP53 mutation carriers reflect cancer-like fragmentation patterns," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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