Tumour Suppressors and Cellular Senescence

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. (c) 2014 IUBMB Life, 66(12):812-822, 2014