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

• Published in: Cancer cell Vol. 10; no. 5; pp. 425 - 435
• Main Authors: Sharma, Sreenath V., Gajowniczek, Patrycja, Way, Inna P., Lee, Diana Y., Jiang, Jane, Yuza, Yuki, Classon, Marie, Haber, Daniel A., Settleman, Jeffrey
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2006
• Subjects: Animals; Apoptosis - physiology; Cell Line, Tumor; Cell Survival; CELLCYCLE; DNA; Enzyme Inhibitors - metabolism; Genes, abl; Humans; Mice; Models, Biological; Neoplasms - metabolism; NIH 3T3 Cells; Phosphoric Monoester Hydrolases - metabolism; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Signal Transduction - physiology; SIGNALING; src-Family Kinases - genetics; src-Family Kinases - metabolism; Temperature; CELLCYCLE; DNA; SIGNALING
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccr.2006.09.014

“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.