Senescence; an endogenous anticancer mechanism.
Summary of "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.
Affiliation
Laboratory of Cellular Signaling and Plasticity, Department of Biophysics and Center of Biotechnology, Federal University of Rio Grande do Sul, Av. Bento Goncalves, 9500, Porto Alegre, Brazil.
Journal Details
This article was published in the following journal.
Name: Frontiers in bioscience : a journal and virtual library
ISSN: 1093-4715
Pages: 2616-43
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22652801
- DOI: http://dx.doi.org/
Medical and Biotech [MESH] Definitions
Aging, Premature
Changes in the organism associated with senescence, occurring at an accelerated rate.
Virus Activation
The mechanism by which latent viruses, such as genetically transmitted tumor viruses (PROVIRUSES) or PROPHAGES of lysogenic bacteria, are induced to replicate and then released as infectious viruses. It may be effected by various endogenous and exogenous stimuli, including B-cell LIPOPOLYSACCHARIDES, glucocorticoid hormones, halogenated pyrimidines, IONIZING RADIATION, ultraviolet light, and superinfecting viruses.
Geriatrics
The branch of medicine concerned with the physiological and pathological aspects of the aged, including the clinical problems of senescence and senility.
Drug Screening Assays, Antitumor
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Xenograft Model Antitumor Assays
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
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