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Unmasking senescence: context-dependent effects of SASP in cancer

Nature Reviews Cancer volume 19, pages 439–453 (2019)Cite this article

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Abstract

Cellular senescence plays a critical role in tumorigenesis. Once thought of as a tissue culture artefact by some researchers, senescence is now a major field of study. Although there are common molecular mechanisms that enforce the growth arrest that characterizes the phenotype, the impact of senescence is varied and can, in some instances, have opposite effects on tumorigenesis. It has become clearer that the cell of origin and the tissue in question dictate the impact of senescence on tumorigenesis. In this Review, we unravel this complexity by focusing on how senescence impacts tumorigenesis when it arises within incipient tumour cells versus stromal cells, and how these roles can change in different stages of disease progression. In addition, we highlight the diversity of the senescent phenotype and its functional output beyond growth arrest: the senescence-associated secretory phenotype (SASP). Fortunately, a number of new genetic and pharmacologic tools have been developed that are now allowing the senescence phenotype to be parsed further.

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Fig. 1: Signalling pathways control senescence-associated secretory phenotype (SASP) expression.
Fig. 2: Senescence-associated secretory phenotype (SASP) factors can support or suppress anti-tumour immune responses.
Fig. 3: Function of senescence-associated secretory phenotype (SASP) factors during tumour initiation and progression.

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Acknowledgements

The work was supported in part by the US Army Medical Research Acquisition Activity, from the awarding and administrating acquisition office at 820 Chandler Street, Fort Detrick MD 21702-5014; by the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program, under Award W81XWH-16-1-0728; and by the US National Institutes of Health, Grant R01 AG059244 01A1. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.

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  1. These authors contributed equally: Douglas V. Faget, Qihao Ren

Authors and Affiliations

  1. Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA

    Douglas V. Faget, Qihao Ren & Sheila A. Stewart

  2. Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Sheila A. Stewart

  3. ICCE Institute, Washington University School of Medicine, St. Louis, MO, USA

    Sheila A. Stewart

  4. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

    Sheila A. Stewart

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Related links

SEER database: https://seer.cancer.gov/explorer/application.php?site=1&data_type=1&graph_type=3&compareBy=sex&chk_sex_1=1&chk_race_1=1&chk_data_type_1=1&advopt_precision=1&showDataFor=race_1_and_data_type_1

Glossary

Incipient tumour cells

Tumour cells at an initial malignant stage.

Senescence-associated secretory phenotype

(SASP). Proteins secreted by senescent cells that act in a paracrine fashion.

Senolytics

Drugs that specifically target and induce death in senescent cells.

Oncogene-induced senescence

(OIS). Senescence induced following overexpression of oncogenes.

Senescence-associated β-galactosidase

(SA-ßGal). Acidic ßGal activity found in senescent cells.

Therapy-induced senescence

(TIS). Senescence induced by anticancer therapeutics.

Replicative senescence

Senescence induced following sequential rounds of cellular division.

Myeloid-derived suppressor cells

Immature myeloid cells that specifically inhibit natural killer and CD8+ T cell killing.

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Faget, D.V., Ren, Q. & Stewart, S.A. Unmasking senescence: context-dependent effects of SASP in cancer. Nat Rev Cancer 19, 439–453 (2019). https://doi.org/10.1038/s41568-019-0156-2

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