Primary mammalian cells reach replicative exhaustion after several passages in vitro, a process called replicative senescence. During such a state of permanent growth arrest, senescent cells are refractory to physiological proliferation stimuli with altered cell morphology and gene expression patterns, although they remain viable with preserved metabolic activity. Interestingly, senescent cells have also been detected in vivo in human tumors, particularly in benign lesions. Tumor suppressor genes are closely involved in senescence, as their knockdown and ectopic expression confer immortality and senescence induction, respectively. By using high throughput genetic screenings to search for genes involved in senescence, several candidate oncogenes and putative tumour suppressor genes have been isolated recently, including subtypes of miRNAs. Senescence is thus an anti-tumorigenic mechanism for avoidance of indefinite cell proliferation when an oncogenic alteration has occurred. In this review, we remark how these findings offer new perspectives in the modulation of senescence and open new approaches for cancer therapy.
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