A common signaling cascade may underlie "addiction" to the Src, BCR-ABL, and EGF receptor oncogenes

Authors:
Sharma SV, Gajowniczek P, Way IP, Lee DY, Jiang J, Yuza Y, Classon M, Haber DA, Settleman J
In:
Source: Cancer Cell
Publication Date: (2006)
Issue: 10(5): 425-35
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
NIH/3T3
Species: mouse
Tissue Origin: embryo
Platform:
Nucleofectorâ„¢ I/II/2b
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.