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Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis

Author

Listed:
  • Zhenbang Chen

    (Cancer Biology and Genetics Program
    Department of Pathology)

  • Lloyd C. Trotman

    (Cancer Biology and Genetics Program
    Department of Pathology)

  • David Shaffer

    (Cancer Biology and Genetics Program
    Sloan-Kettering Institute)

  • Hui-Kuan Lin

    (Cancer Biology and Genetics Program
    Department of Pathology)

  • Zohar A. Dotan

    (Cancer Biology and Genetics Program
    Department of Pathology)

  • Masaru Niki

    (Cancer Biology and Genetics Program
    Department of Pathology)

  • Jason A. Koutcher

    (Sloan-Kettering Institute)

  • Howard I. Scher

    (Sloan-Kettering Institute)

  • Thomas Ludwig

    (Columbia University)

  • William Gerald

    (Department of Pathology)

  • Carlos Cordon-Cardo

    (Department of Pathology)

  • Pier Paolo Pandolfi

    (Cancer Biology and Genetics Program
    Department of Pathology)

Abstract

Cell senescence and cancer Cellular senescence, a growth-arrest program that limits the lifespan of mammalian cells and prevents unlimited cell proliferation, is attracting considerable interest because of its links to tumour suppression. Using a mouse model in which the oncogene Ras is activated in the haematopoietic compartment of bone marrow, Braig et al. show that cellular senescence can block lymphoma development. Genetic inactivation of the histone methyltransferase Suv39h1 that controls senescence by ‘epigenetic’ modification of DNA-associated proteins, or a pharmacological approach that mimics loss of this enzyme, allow the formation of malignant lymphomas in response to oncogenic Ras. This work has important implications for both tumour development and tumour therapy. Michaloglou et al. report that oncogene-induced senescence may be a physiologically important process in humans, keeping moles in a benign state for many years: unchecked they develop into malignant melanomas. Chen et al. also find that cellular senescence blocks tumorigenesis in vivo: they show that acting together, the p53 tumour suppressor and the cellular senescence system can prevent prostate cancer induction in mice by the PTEN mutation. Collado et al. show that cellular senescence is a defining feature of Ras-initiated premalignant tumours; this could prove valuable in the diagnosis and prognosis of cancer. See the web focus .

Suggested Citation

  • Zhenbang Chen & Lloyd C. Trotman & David Shaffer & Hui-Kuan Lin & Zohar A. Dotan & Masaru Niki & Jason A. Koutcher & Howard I. Scher & Thomas Ludwig & William Gerald & Carlos Cordon-Cardo & Pier Paolo, 2005. "Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis," Nature, Nature, vol. 436(7051), pages 725-730, August.
  • Handle: RePEc:nat:nature:v:436:y:2005:i:7051:d:10.1038_nature03918
    DOI: 10.1038/nature03918
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    Cited by:

    1. 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.
    2. Ni Li & Qiuli Liu & Ying Han & Siyu Pei & Bisheng Cheng & Junyu Xu & Xiang Miao & Qiang Pan & Hanling Wang & Jiacheng Guo & Xuege Wang & Guoying Zhang & Yannan Lian & Wei Zhang & Yi Zang & Minjia Tan , 2022. "ARID1A loss induces polymorphonuclear myeloid-derived suppressor cell chemotaxis and promotes prostate cancer progression," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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