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Novel ARF/p53-independent senescence pathways in cancer repression

Journal of Molecular Medicine volume 89, pages 857–867 (2011)Cite this article

Abstract

Cellular senescence, which can be induced by various stimuli, is a stress response that manifests as irreversible cell cycle arrest. Recent studies have revealed that cellular senescence can serve as a critical barrier for cancer development. Induction of cellular senescence by oncogenic insults, such as Ras overexpression or by inactivation of PTEN tumor suppressor, triggers an ARF/p53-dependent tumor-suppressive effect which can significantly restrict cancer progression. Given the important role of the ARF/p53 pathway in cellular senescence and tumor suppression, drugs that stabilize p53 expression have been developed and tested in clinical trials. However, a major hurdle for p53 targeting in cancer treatment arises from the frequent deficiency or mutation of ARF or p53 in human cancers, which, in turn, profoundly compromises their tumor-suppressive ability. Recent discoveries of novel regulators involved in ARF/p53-independent cellular senescence not only reveal novel paradigms for cellular senescence but also provide alternative approaches for cancer therapy.

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Acknowledgments

We apologize to all the scientists whose great works are not cited in this review due to the limited space. We thank the members of Dr. Lin's lab for their discussion and Sunita Patterson from MD Anderson's Department of Scientific Publications for the editing. This work is supported in part by National Institutes of Health grants (R01CA136787-01A2 and R01CA149321-01), MD Anderson Trust Scholar Fund, a grant from Cancer Prevention Research Institute of Texas and by a New Investigator Award from the Department of Defense (PC081292) to H.K. Lin.

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The authors declare no competing financial interests.

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Affiliations

  1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Chia-Hsin Chan, Yuan Gao, Asad Moten & Hui-Kuan Lin

  2. The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, 77030, USA

    Yuan Gao & Hui-Kuan Lin

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  1. Chia-Hsin Chan
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  2. Yuan Gao
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  3. Asad Moten
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  4. Hui-Kuan Lin
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Correspondence to Hui-Kuan Lin.

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Chan, CH., Gao, Y., Moten, A. et al. Novel ARF/p53-independent senescence pathways in cancer repression. J Mol Med 89, 857–867 (2011). https://doi.org/10.1007/s00109-011-0766-y

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  • DOI: https://doi.org/10.1007/s00109-011-0766-y

Keywords

  • Skp2
  • p53
  • Cellular senescence
  • Cancer therapy