Senescence in premalignant tumours (original) (raw)

Tumour biology

Nature volume 436, page 642 (2005)Cite this article

Abstract

Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development1,2, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer.

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Figure 1: Premalignant lung adenomas induced by oncogenic K-ras are positive for markers of senescence, whereas malignant adenocarcinomas are negative.

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Authors and Affiliations

  1. Spanish National Cancer Centre (CNIO), Madrid, 28029, Spain
    Manuel Collado, Alejo Efeyan, Carmen Guerra, Alberto J. Schuhmacher, Marta Barradas, Mariano Barbacid & Manuel Serrano
  2. MRC Clinical Sciences Centre, Imperial College, Hammersmith, London, W12 0NN, UK
    Jesús Gil
  3. Spanish National Centre of Biotechnology (CNB-CSIC), Madrid, 28049, Spain
    Alberto Benguría & Angel Zaballos
  4. Department of Animal Surgery and Medicine, Complutense University, Madrid, 28040, Spain
    Juana M. Flores
  5. Centre for Cutaneous Research, Institute of Cell and Molecular Science, London, E1 2AT, UK
    David Beach

Authors

  1. Manuel Collado
  2. Jesús Gil
  3. Alejo Efeyan
  4. Carmen Guerra
  5. Alberto J. Schuhmacher
  6. Marta Barradas
  7. Alberto Benguría
  8. Angel Zaballos
  9. Juana M. Flores
  10. Mariano Barbacid
  11. David Beach
  12. Manuel Serrano

Corresponding author

Correspondence toManuel Serrano.

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Competing interests

The authors declare no competing financial interests.

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Collado, M., Gil, J., Efeyan, A. et al. Senescence in premalignant tumours.Nature 436, 642 (2005). https://doi.org/10.1038/436642a

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Editorial Summary

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.

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