Tumour suppressors and cellular senescence

Abstract

Cellular senescence is a stable cell cycle arrest that normal cells undergo in response to a variety of intrinsic and extrinsic stimuli, including progressive telomere shortening, changes in telomeric structure or other forms of genotoxic as well nongenotoxic stress. Senescence is thought to have originated as a remodelling program that is active in embryonic development and acts as a key tumour suppressor mechanism during the reproductive stage in early adult life, by leading to the removal of potentially cancerous cells. However, in later adult life, it promotes organismal aging by compromising tissue repair and regeneration due to the accumulation of senescent cells, depletion of stem/progenitor cells and secretion of an array of inflammatory cytokines, chemokines and matrix metalloproteases. Whilst suppressing tumour formation in the senescent cells, these inflammatory cytokines, chemokines and metalloproteases can promote tumour progression and metastasis in the neighbouring cells. Herein, we review the molecular pathways that underlie cellular senescence and how it contributes towards tumour suppression. V C 2014 IUBMB Life, 66(12):812-822, 2014

ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases

“…In conclusion, cell senescence reduces the age-related tumor development and contributes to human aging, suggesting that aging might be switched for tumorigenesis [ 201 , 202 ]. ROS may modulate tumor suppression process, which is induced by the senescence, thus participating in anticancer mechanisms, although ROS may act as tumor promoters in definite conditions [ 48 ].…”

Senescence in the aging process

“…Although senescent cells play an important role in tumour suppression and some unsuspected aspects of normal physiology 48 – 50 , they are central players both in age-related mortality and in various forms of morbidity (for example, as causal agents of adverse reactions to chemotherapy). However, data on their phenotype and behaviour fall far short of what is required if therapeutic progress is to be made in a reasonable timescale.…”

Regulation of lung endothelial permeability by NEK kinases

“…5 p53 is a transcription factor which was initially identified as an oncogene. 6 Further studies have confirmed that it is a tumor suppressor 7 associated with anti-inflammatory activities. 8 Indeed, p53 attenuates NF-kappaB activation and ALI.…”

“…The understanding of those molecular cascades which govern the permeability of the vascular wall; may reveal novel ways to counteract ARDS . p53 is a transcription factor which was initially identified as an oncogene . Further studies have confirmed that it is a tumor suppressor associated with anti‐inflammatory activities .…”