Breaking news: high-speed race ends in arrest--how oncogenes induce senescence.
Oncogene activation in normal cells induces a permanent proliferative arrest known as cellular senescence. This phenomenon restrains the expansion of cells that bear an activated oncogene and acts as a powerful tumor-suppressive process. Although the full molecular mechanisms are still being elucidated, it has been observed recently that some oncogenes alter the DNA-replication process and cause DNA-damage accumulation. DNA-damage checkpoint-response activation together with the increased appearance of heterochromatin formation that leads to transcriptional silencing of proliferative genes are, presently, the two main mechanisms known that establish and maintain oncogene-induced senescence. Here, we discuss the most recent advancements in understanding the molecular and cellular mechanisms that control cellular senescence caused by oncogene activation and their impact on cancer studies.
Di Micco
Raffaella
R
IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, via Adamello 16, 20139 Milan, Italy.
Fumagalli
Marzia
M
d'Adda di Fagagna
Fabrizio
F
D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D006801:Humans; D009857:Oncogenes / Q000502:physiology*