A Common Signaling Cascade May Underlie "Addiction" to the Src, BCR-ABL, and EGF Receptor Oncogenes

Cancer Cell. 2006 Nov;10(5):425-35. doi: 10.1016/j.ccr.2006.09.014.

Abstract

"Oncogene addiction" describes an unexplained dependency of cancer cells on a particular cellular pathway for survival or proliferation. We report that differential attenuation rates of prosurvival and proapoptotic signals in oncogene-dependent cells contribute to cell death following oncogene inactivation. Src-, BCR-ABL-, and EGF receptor-dependent cells exhibit a similar profile of signal attenuation following oncogene inactivation characterized by rapid diminution of phospho-ERK, -Akt, and -STAT3/5, and a delayed accumulation of the proapoptotic effector phospho-p38 MAPK. These findings implicate a transient imbalance in survival and apoptotic oncogenic outputs in the apoptotic response to oncogene inactivation. Moreover, these observations implicate a common profile of signal attenuation for multiple oncogenes and suggest that "addiction" associated with apoptosis reflects an active rather than a passive process.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Survival
  • Enzyme Inhibitors / metabolism
  • ErbB Receptors* / genetics
  • ErbB Receptors* / metabolism
  • Genes, abl*
  • Humans
  • Mice
  • Models, Biological
  • NIH 3T3 Cells
  • Neoplasms / metabolism*
  • Phosphoric Monoester Hydrolases / metabolism
  • Signal Transduction / physiology*
  • Temperature
  • src-Family Kinases* / genetics
  • src-Family Kinases* / metabolism

Substances

  • Enzyme Inhibitors
  • ErbB Receptors
  • src-Family Kinases
  • Phosphoric Monoester Hydrolases