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Switch of glycolysis to gluconeogenesis by dexamethasone for treatment of hepatocarcinoma

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  • Ruihua Ma

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Wanguang Zhang

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Ke Tang

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Huafeng Zhang

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Yi Zhang

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Dapeng Li

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Yong Li

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Pingwei Xu

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Shunqun Luo

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Wenqian Cai

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Tiantian Ji

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Foad Katirai

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Duyun Ye

    (Tongji Medical College, Huazhong University of Science and Technology)

  • Bo Huang

    (Tongji Medical College, Huazhong University of Science and Technology
    National Key Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences)

Abstract

Gluconeogenesis is a fundamental feature of hepatocytes. Whether this gluconeogenic activity is also present in malignant hepatocytes remains unexplored. A better understanding of this biological process may lead to novel therapeutic strategies. Here we show that gluconeogenesis is not present in mouse or human malignant hepatocytes. We find that two critical enzymes 11β-HSD1 and 11β-HSD2 that regulate glucocorticoid activities are expressed inversely in malignant hepatocytes, resulting in the inactivation of endogenous glucocorticoids and the loss of gluconeogenesis. In patients’ hepatocarcinoma, the expression of 11β-HSD1 and 11β-HSD2 is closely linked to prognosis and survival. Dexamethasone, an active form of synthesized glucocorticoids, is capable of restoring gluconeogenesis in malignant cells by bypassing the abnormal regulation of 11β-HSD enzymes, leading to therapeutic efficacy against hepatocarcinoma. These findings clarify the molecular basis of malignant hepatocyte loss of gluconeogenesis and suggest new therapeutic strategies.

Suggested Citation

  • Ruihua Ma & Wanguang Zhang & Ke Tang & Huafeng Zhang & Yi Zhang & Dapeng Li & Yong Li & Pingwei Xu & Shunqun Luo & Wenqian Cai & Tiantian Ji & Foad Katirai & Duyun Ye & Bo Huang, 2013. "Switch of glycolysis to gluconeogenesis by dexamethasone for treatment of hepatocarcinoma," Nature Communications, Nature, vol. 4(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3508
    DOI: 10.1038/ncomms3508
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