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

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.

Directing adipose‐derived stem cells into keratinocyte‐like cells: impact of medium composition and culture condition

“…A main obstacle in this procedure is the acquisition of autologous skin cells – a sufficient amount of intact skin tissue must be obtained typically by dermabrasion or incision – which bears the risk of developing pain, scarring, infection and slow healing at the donor site . Moreover, keratinocytes, different from fibroblasts, require specific culture conditions and the majority of keratinocytes become senescent after only 10–20 doublings, which hampers the production of enough viable cells for transplantation. The breakthrough discovery that ASC within white fat can transdifferentiate to a large array of cell species including keratinocyte‐like cells opens a new road for the above‐mentioned procedure.…”

Single-Strand Break End Resection in Genome Integrity: Mechanism and Regulation by APE2

“…It has been shown recently in senescent epithelial cells that ROS induces more SSBs and downregulates PARP1 expression, leading to defective SSB repair and emergence of post-senescent transformed and mutated precancerous cells [5]. Thus, the mutagenicity of accumulated unrepaired SSBs in epithelial cells is proposed as the driver of cancer development [62]. APE2 mutants have been found in several cancer patients, suggesting that defective SSB end resection is implicated in cancer development [19].…”

miR‑106b‑5p promotes cell proliferation and cell cycle progression by directly targeting CDKN1A in osteosarcoma

“…Cyclin-dependent kinase inhibitors are known to exert effects by binding to CDK monomers or CDK/cyclin complexes (31). As a universal inhibitor (especially the CDK4/6-cyclin D complexes in G1 phase), CDKN1A serves a significant role in a p53-dependent and independent manner, leading to G0/G1 extension and suppression of further cell proliferation (32).…”