Oncogene-induced senescence: the bright and dark side of the response.
In late 1990s, it was shown that activated oncogenes are able to induce senescence. Since then large leaps in understanding this phenomenon have been achieved. There is substantial evidence supporting oncogene-induced senescence (OIS) as a potent antitumor barrier in vivo. Multiple pathways participating in cell cycle regulation, DNA damage signaling, immune response, and bioenergetics regulate the process. Despite its beneficial effects the senescent cell is thought to promote carcinogenesis and age-related disease in a nonautonomous manner. Here, we highlight the works dealing with all these aspects and discuss the studies proposing therapeutic exploitation of OIS.
Gorgoulis
Vassilis G
VG
Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece. vgorg@med.uoa.gr
Halazonetis
Thanos D
TD
D000818:Animals; D001343:Autophagy; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D009857:Oncogenes; D010641:Phenotype; D015398:Signal Transduction / Q000235:genetics