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MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer

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Listed:
  • Peter C. Hart

    (University of Illinois at Chicago
    University of Illinois at Chicago)

  • Mao Mao

    (University of Illinois at Chicago
    University of Illinois at Chicago)

  • Andre Luelsdorf P. de Abreu

    (University of Illinois at Chicago
    University of Illinois at Chicago
    Universidade Estadual de Maringa)

  • Kristine Ansenberger-Fricano

    (University of Illinois at Chicago
    University of Illinois at Chicago)

  • Dede N. Ekoue

    (University of Illinois at Chicago)

  • Douglas Ganini

    (Free Radical Metabolite Section, Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences/NIH)

  • Andre Kajdacsy-Balla

    (University of Illinois at Chicago)

  • Alan M. Diamond

    (University of Illinois at Chicago)

  • Richard D. Minshall

    (University of Illinois at Chicago
    University of Illinois at Chicago)

  • Marcia E. L. Consolaro

    (Universidade Estadual de Maringa)

  • Janine H. Santos

    (University of Medicine and Dentistry of New Jersey)

  • Marcelo G. Bonini

    (University of Illinois at Chicago
    University of Illinois at Chicago
    University of Illinois at Chicago)

Abstract

Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the types of reactive oxygen species egressing from the organelle to affect cellular signalling. Here we demonstrate that MnSOD upregulation in cancer cells establishes a steady flow of H2O2 originating from mitochondria that sustains AMP-activated kinase (AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics. Recapitulating in vitro findings, clinical and epidemiologic analyses of MnSOD expression and AMPK activation indicated that the MnSOD/AMPK pathway is most active in advanced stage and aggressive breast cancer subtypes. Taken together, our results indicate that MnSOD serves as a biomarker of cancer progression and acts as critical regulator of tumour cell metabolism.

Suggested Citation

  • Peter C. Hart & Mao Mao & Andre Luelsdorf P. de Abreu & Kristine Ansenberger-Fricano & Dede N. Ekoue & Douglas Ganini & Andre Kajdacsy-Balla & Alan M. Diamond & Richard D. Minshall & Marcia E. L. Cons, 2015. "MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7053
    DOI: 10.1038/ncomms7053
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