RAS unplugged: negative feedback and oncogene-induced senescence.
Many normal cells respond to certain stresses, such as oncogene activation, by undergoing a permanent form of growth arrest known as senescence, an intrinsic tumor suppressor program. The predominant view has been that senescence is caused in some settings through a mutant oncogene's ability to induce activation of high levels of sustained MAP kinase and PI3 kinase signaling. A new study in this issue of Cancer Cell has challenged this model with the surprising finding that aberrant activation of the RAS/RAF pathway can induce a negative feedback loop that globally attenuates MAPK and PI3K signaling and that the reduction of signaling in these pathways is required for senescence.
Bardeesy
Nabeel
N
Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts 02114, USA. nelbardeesy@partners.org
Sharpless
Norman E
NE
D000818:Animals; D016922:Cellular Senescence; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D011905:Genes, ras / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases