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Oncogene-Induced Senescence (OIS) as a Cellular Response to Oncogenic Stresses

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Cellular Senescence and Tumor Suppression

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Abstract

Oncogene-Induced Senescence (OIS) is a tumor suppressor mechanism that prevents the expansion of cells bearing activated oncogenes. Two major tumor suppressors control OIS: p53 and Rb. These tumor suppressors are not activated to regulate senescence by normal growth signals, but by stress signals caused by activated oncogenes. The activation of p53 by oncogenes involves reactive oxygen species (oxidative stress), DNA replication stress and the DNA damage response. The activation of Rb during OIS is less understood, but it involves Cyclin-Dependent Kinases (CDKs) inhibitors such as p21 and p16INK4a or the downregulation of CDK4, due to a decrease in Myc functions. Rb also controls the formation of heterochromatin in senescent cells, and this process has been linked to p16INK4a, p21 and the promyelocytic leukemia protein PML. The process of OIS occurs in both rodents and humans, but its control by p53 and Rb differ between these species. In rodents, senescence can be inactivated by disabling the p53 or the Rb pathway. In contrast, human cells can organize p53 or Rb-independent senescence. OIS is initiated as a cell autonomous process in response to oncogenes, but it also involves secreted cytokines. The mechanistic understanding of OIS suggests novel strategies to treat human cancers.

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Abbreviations

ARF:

Refers to p19ARF in mice and p14ARF in humans. The ARF open reading frame overlaps with the p16INK4a reading frame. Hence, ARF is an abbreviation of alternative reading frame

CKI:

Cyclin-dependent kinase inhibitor

DDR:

DNA damage response

OIS:

Oncogene-induced senescence

ROS:

Reactive oxygen species

SAHF:

Senescence-associated heterochromatin foci

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Acknowledgements

GF is a senior FRSQ fellow.

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Authors and Affiliations

  1. Département de Biochimie, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, Québec, Canada, H3C 3J7

    Véronique Bourdeau & Gerardo Ferbeyre

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  1. Véronique Bourdeau
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  2. Gerardo Ferbeyre
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Correspondence to Gerardo Ferbeyre .

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Editors and Affiliations

  1. Cancer Research UK, University of Glasgow, Switchback Road, Glasgow, G61 1BD, United Kingdom

    Peter D. Adams

  2. Dept. Molecular & Cell Biology &, Brown University, Ship Street 70, Providence, 02912, U.S.A.

    John M. Sedivy

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Bourdeau, V., Ferbeyre, G. (2010). Oncogene-Induced Senescence (OIS) as a Cellular Response to Oncogenic Stresses. In: Adams, P., Sedivy, J. (eds) Cellular Senescence and Tumor Suppression. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1075-2_3

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