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Epithelial-Mesenchymal Transition Induced by Senescent Fibroblasts

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Cancer Microenvironment

Abstract

Depending on the cell type and tissue environment, epithelial and mesenchymal cell phenotypes are not static and can be highly dynamic. Epithelial-mesenchymal transitions (EMTs) and reverse EMTs provide flexibility during embryogenesis. While EMTs are a critical normal process during development and wound healing, properties of the EMT have been implicated in human pathology, particularly cancer metastasis. A normal undamaged epithelium does not typically exhibit features of an EMT. However, particularly under the influence of the surrounding microenvironment, cancer cells may reactivate developmental phenotypes out of context in the adult. This reactivation, such as the EMT, can facilitate tumor cell invasion and metastasis, and therefore is a major mechanism of tumor progression. Conversely, cellular senescence, which is associated with aging, is a process by which cells enter a state of permanent cell cycle arrest, thereby constituting a potent tumor suppressive mechanism. However, accumulating evidence shows that senescent cells can have deleterious effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescence-associated secretory phenotype (SASP) that turns senescent fibroblasts into pro-inflammatory cells having the ability to promote tumor progression, in part by inducing an EMT in nearby epithelial cells. Here, we summarize the potential impacts of SASP factors, particularly interleukins, on tissue microenvironments and their ability to stimulate tumor progression through induction of an EMT.

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Acknowledgments

The authors wish to thank Dr. Andrew P. Smith for editing the manuscript.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA, 94945, USA

    Remi-Martin Laberge, Pierre Awad, Judith Campisi & Pierre-Yves Desprez

  2. California Pacific Medical Center, Research Institute, 475 Brannan Street, San Francisco, CA, 94107, USA

    Pierre-Yves Desprez

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  1. Remi-Martin Laberge
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  2. Pierre Awad
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Correspondence to Pierre-Yves Desprez.

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Laberge, RM., Awad, P., Campisi, J. et al. Epithelial-Mesenchymal Transition Induced by Senescent Fibroblasts. Cancer Microenvironment 5, 39–44 (2012). https://doi.org/10.1007/s12307-011-0069-4

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