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Off and back-on again: a tumor suppressor’s tale

Oncogene volume 37, pages 3058–3069 (2018)Cite this article

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Abstract

Tumor suppressor genes play critical roles orchestrating anti-cancer programs that are both context dependent and mechanistically diverse. Beyond canonical tumor suppressive programs that control cell division, cell death, and genome stability, unexpected tumor suppressor gene activities that regulate metabolism, immune surveillance, the epigenetic landscape, and others have recently emerged. This diversity underscores the important roles these genes play in maintaining cellular homeostasis to suppress cancer initiation and progression, but also highlights a tremendous challenge in discerning precise context-specific programs of tumor suppression controlled by a given tumor suppressor. Fortunately, the rapid sophistication of genetically engineered mouse models of cancer has begun to shed light on these context-dependent tumor suppressor activities. By using techniques that not only toggle “off” tumor suppressor genes in nascent tumors, but also facilitate the timely restoration of gene function “back-on again” in disease specific contexts, precise mechanisms of tumor suppression can be revealed in an unbiased manner. This review discusses the development and implementation of genetic systems designed to toggle tumor suppressor genes off and back-on again and their potential to uncover the tumor suppressor’s tale.

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Acknowledgements

We would like to thank Junwei Shi, Donita Brady, and the entire Feldser Laboratory for critical review of this manuscript. D.F. is the Alan Steinberg Scholar in Cancer Research, and a Richard A. “Buz” Cooper Scholar of the Abramson Cancer Center. Work in the Feldser Laboratory is supported by grants from the American Lung Association LCD-400095, NIH CA193602, CA205340, and also by Penn Medicine’s Abramson Cancer Center core grant P30-CA016520.

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Authors and Affiliations

  1. Biomedical Graduate Studies Program in Cellular and Molecular Biology, Perelman School of Medicine, University of Pennsylvania, 421 Curie Blvd., 751 BRB II/III, Philadelphia, PA, 19104-6160, USA

    Jonuelle Acosta & David M. Feldser

  2. Vagelos Scholars Program, School of Arts and Sciences, University of Pennsylvania, 421 Curie Blvd., 751 BRB II/III, Philadelphia, PA, 19104-6160, USA

    Walter Wang

  3. Department of Cancer Biology, University of Pennsylvania, 421 Curie Blvd., 751 BRB II/III, Philadelphia, PA, 19104-6160, USA

    David M. Feldser

  4. Abramson Family Cancer Research Institute, University of Pennsylvania, 421 Curie Blvd., 751 BRB II/III, Philadelphia, PA, 19104-6160, USA

    David M. Feldser

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  1. Jonuelle Acosta
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Correspondence to David M. Feldser.

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Acosta, J., Wang, W. & Feldser, D.M. Off and back-on again: a tumor suppressor’s tale. Oncogene 37, 3058–3069 (2018). https://doi.org/10.1038/s41388-018-0186-3

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