Senescence; an endogenous anticancer mechanism.
Pre-malignant tumor cells enter a state of irreversible cell cycle arrest termed senescence (cellular senescence; CS). CS is a part of the aging program and involves multiple signaling cascades and transduction mechanisms. In general, senescence can be divided into replicative senescence and premature senescence. Replicative senescence (replicative CS) has been described for all metabolically active cells that undergo a spontaneous decline in growth rate. Notably, ectopic expression of telomerase holoenzyme (hTert) can prevent replicative CS. In cancer cells, premature senescence induced by oncogenes, named oncogene-induced senescence (oncogene induced CS; OIS), play an important role in preventing the development of cancer. Oncogene induced CS can be promoted by the loss of tumor suppressor genes, such as PTEN. Additionally, other interesting mechanisms, like selective microRNA expression, epigenetic modifications, or even stress conditions, are also able to activate the senescence program. Here, we will critically review the literature on the role of senescence in preventing the development of cancer and discuss the potential of senescence modulation for generating new molecular tools that could be explored as anticancer treatments.
Department of Biophysics and Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Jose
J
Vargas
Bruno Cesar
BC
Feltes
Joice de Faria
Jde F
Poloni
Guido
G
Lenz
Diego
D
Bonatto
D000818:Animals; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D042822:Genomic Instability; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D009857:Oncogenes; D018384:Oxidative Stress; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D059506:Telomere Shortening / Q000235:genetics
D035683:MicroRNAs; D019098:Telomerase