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Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis

Author

Listed:
  • Gina M. DeNicola

    (Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
    Abramson Family Cancer Research Institute, University of Pennsylvania)

  • Florian A. Karreth

    (Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
    University of Vienna, Dr. Bohrgasse 9, 1030 Vienna, Austria)

  • Timothy J. Humpton

    (Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK)

  • Aarthi Gopinathan

    (Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK
    Abramson Family Cancer Research Institute, University of Pennsylvania)

  • Cong Wei

    (Center for Cancer Pharmacology, University of Pennsylvania)

  • Kristopher Frese

    (Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK)

  • Dipti Mangal

    (Center for Cancer Pharmacology, University of Pennsylvania)

  • Kenneth H. Yu

    (Center for Cancer Pharmacology, University of Pennsylvania)

  • Charles J. Yeo

    (Jefferson Medical College)

  • Eric S. Calhoun

    (Alma College)

  • Francesca Scrimieri

    (The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions)

  • Jordan M. Winter

    (The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions)

  • Ralph H. Hruban

    (The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions
    The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions)

  • Christine Iacobuzio-Donahue

    (The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions
    The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions)

  • Scott E. Kern

    (The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions
    The Sol Goldman Pancreatic Cancer Research Center, the Johns Hopkins Medical Institutions)

  • Ian A. Blair

    (Center for Cancer Pharmacology, University of Pennsylvania)

  • David A. Tuveson

    (Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK)

Abstract

Radical role reversal Reactive oxygen species (ROS), such as free radicals, are mutagenic and might therefore be expected to promote tumorigenesis. However, this work shows that expression of the oncogenes Kras, Braf and Myc at endogenous levels in mouse cells in fact reduces ROS levels. Some oncogenes are also shown to induce the transcription factor Nrf2, which acts to detoxify ROS. In line with this finding, deletion of Nrf2 impairs K-Ras-induced pancreatic tumour formation. Modulation of the redox state in cells thus seems to be an important factor in determining tumorigenic potential, and may be a possible target for therapy.

Suggested Citation

  • Gina M. DeNicola & Florian A. Karreth & Timothy J. Humpton & Aarthi Gopinathan & Cong Wei & Kristopher Frese & Dipti Mangal & Kenneth H. Yu & Charles J. Yeo & Eric S. Calhoun & Francesca Scrimieri & J, 2011. "Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis," Nature, Nature, vol. 475(7354), pages 106-109, July.
    • Handle: RePEc:nat:nature:v:475:y:2011:i:7354:d:10.1038_nature10189
    DOI: 10.1038/nature10189
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    Cited by:

    1. Athanasios Valavanidis & Thomais Vlachogianni & Konstantinos Fiotakis & Spyridon Loridas, 2013. "Pulmonary Oxidative Stress, Inflammation and Cancer: Respirable Particulate Matter, Fibrous Dusts and Ozone as Major Causes of Lung Carcinogenesis through Reactive Oxygen Species Mechanisms," IJERPH, MDPI, vol. 10(9), pages 1-22, August.
    2. Weiqiang Lu & Jiayan Cui & Wanyan Wang & Qian Hu & Yun Xue & Xi Liu & Ting Gong & Yiping Lu & Hui Ma & Xinyu Yang & Bo Feng & Qi Wang & Naixia Zhang & Yechun Xu & Mingyao Liu & Ruth Nussinov & Feixion, 2024. "PPIA dictates NRF2 stability to promote lung cancer progression," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Rana Salam & Alexa Saliou & Franck Bielle & Mathilde Bertrand & Christophe Antoniewski & Catherine Carpentier & Agusti Alentorn & Laurent Capelle & Marc Sanson & Emmanuelle Huillard & Léa Bellenger & , 2023. "Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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