Abstract
Normal cells possess a limited proliferative life span, after which they enter a state of irreversible growth arrest, called replicative senescence, which acts as a potent barrier against transformation. Transformed cells have escaped the process of replicative senescence and theoretically can not re-enter senescence. However, recent observations showed that transformed cells, and particularly the melanoma cells, can still undergo oncogene or stress-induced senescence. This senescence state is accompanied by many of the markers associated with replicative senescence, such as flattened shape, increased acidic β-galactosidase activity, characteristic changes in gene expression and growth arrest. Interestingly, in some cancers, senescence induction following chemotherapy has been correlated with a favorable patient outcome. In this review, we gathered recent results describing senescence-like phenotype induction in melanoma cells and discuss why senescence may also be exploited as a therapeutic strategy in melanoma.
© 2011 John Wiley & Sons A/S.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Biomarkers / metabolism
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Cell Cycle
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Cell Proliferation
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Cellular Senescence / physiology*
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Melanoma / pathology
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Melanoma / physiopathology*
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Microphthalmia-Associated Transcription Factor / genetics
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Microphthalmia-Associated Transcription Factor / metabolism
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism
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Oncogenes
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Phenotype
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Poly-ADP-Ribose Binding Proteins
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism
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Syk Kinase
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / metabolism
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / metabolism
Substances
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Biomarkers
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Chromosomal Proteins, Non-Histone
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Cyclin-Dependent Kinase Inhibitor p21
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DEK protein, human
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Intracellular Signaling Peptides and Proteins
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Microphthalmia-Associated Transcription Factor
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Oncogene Proteins
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Poly-ADP-Ribose Binding Proteins
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Proto-Oncogene Proteins c-myc
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T-Box Domain Protein 2
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T-Box Domain Proteins
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Tumor Suppressor Proteins
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase