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Epithelial cell senescence: an adaptive response to pre-carcinogenic stresses?

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Abstract

Senescence is a cell state occurring in vitro and in vivo after successive replication cycles and/or upon exposition to various stressors. It is characterized by a strong cell cycle arrest associated with several molecular, metabolic and morphologic changes. The accumulation of senescent cells in tissues and organs with time plays a role in organismal aging and in several age-associated disorders and pathologies. Moreover, several therapeutic interventions are able to prematurely induce senescence. It is, therefore, tremendously important to characterize in-depth, the mechanisms by which senescence is induced, as well as the precise properties of senescent cells. For historical reasons, senescence is often studied with fibroblast models. Other cell types, however, much more relevant regarding the structure and function of vital organs and/or regarding pathologies, are regrettably often neglected. In this article, we will clarify what is known on senescence of epithelial cells and highlight what distinguishes it from, and what makes it like, replicative senescence of fibroblasts taken as a standard.

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Abbreviations

BER:

Base excision repair

BPEC:

Breast primary epithelial cell

CKI:

Cyclin-dependent kinase inhibitor

DDR:

DNA damage response

DSB:

Double-strand break

EMT:

Epithelium-to-mesenchyme transition

HMEC:

Human mammary epithelial cell

NHEK:

Normal human epidermal keratinocyte

NHOK:

Normal human oral keratinocyte

OIS:

Oncogene-induced senescence

PARP1:

Poly(ADP)ribose polymerase 1

PD:

Population doubling

PSNE:

Post-senescence neoplastic emergence

ROS:

Reactive oxygen species

RS:

Replicative senescence

SA-β-Gal:

Senescence-associated-β-galactosidase activity

SAHF:

Senescence-associated heterochromatin foci

SASP:

Senescence-associated secretory phenotype

SIPS:

Stress-induced premature senescence

SMS:

Senescence messaging secretome

SSB:

Single-strand break

SSBR:

Single-strand break repair

TIS:

Therapy-induced senescence

UPR:

Unfolded protein response

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Acknowledgements

We thank Joe Nassour for critical reading of the manuscript. This work was supported by the Centre National de la Recherche Scientifique, the Université Lille 1, the Université Lille 2, the Ligue contre le Cancer (Comité du Pas-de-Calais and Comité de la Somme), the Institut Pasteur de Lille, and the SIRIC OncoLille (Grant INCa-DGOS-Inserm 6041).

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  1. Univ. Lille, CNRS, Institut Pasteur de Lille, UMR 8161-M3T-Mechanisms of Tumorigenesis and Targeted Therapies, 59000, Lille, France

    Corinne Abbadie, Olivier Pluquet & Albin Pourtier

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  1. Corinne Abbadie
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  2. Olivier Pluquet
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  3. Albin Pourtier
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Correspondence to Corinne Abbadie.

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Abbadie, C., Pluquet, O. & Pourtier, A. Epithelial cell senescence: an adaptive response to pre-carcinogenic stresses?. Cell. Mol. Life Sci. 74, 4471–4509 (2017). https://doi.org/10.1007/s00018-017-2587-9

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  • DOI: https://doi.org/10.1007/s00018-017-2587-9

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