RAS unplugged: negative feedback and oncogene-induced senescence

Cancer Cell. 2006 Dec;10(6):451-3. doi: 10.1016/j.ccr.2006.11.015.


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.

Publication types

  • Comment

MeSH terms

  • Animals
  • Cellular Senescence*
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Genes, ras / physiology*
  • Humans
  • MAP Kinase Signaling System
  • Phosphatidylinositol 3-Kinases / physiology
  • Reactive Oxygen Species / metabolism


  • Reactive Oxygen Species
  • Phosphatidylinositol 3-Kinases
  • Extracellular Signal-Regulated MAP Kinases