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Oncogenic signalling

Mysteries of addiction

Nature Reviews Cancer volume 7, page 4 (2007)Cite this article

The researchers propose (as published in Clinical Cancer Research) that the oncoproteins that maintain a cancer cell have both pro-survival and pro-apoptotic effects on a cell. They suggest that when the activity of a single oncoprotein is disrupted, the pro-survival signals are attenuated faster than pro-apoptotic signals, and that this is enough to temporarily shift the balance in favour of apoptosis.

Now, in Cancer Cell, the authors have empirical evidence to support this idea. They measured the pro-apoptotic and pro-survival factors in several cell culture models — a cell line dependent on the BCR-ABL oncoprotein, a cell line dependent on mutationally activated epidermal growth factor receptor (EGFR), and a non-small cell lung cancer cell line with an activating mutation within EGFR. When the oncogenes were inactivated, the levels of pro-survival factors (Akt, signal transducer and activator of transcription 5 and extracellular-signal regulated kinase 1 and 2) quickly fell, whereas the levels of a pro-apoptotic factor (the activated form of the p38 mitogen-activated protein kinase (phospho-p38)) accumulated, followed by rapid apoptosis.

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References

ORIGINAL RESEARCH PAPER

  1. Sharma, S. V. et al. A common signalling cascade may underlie 'addiction' to the Src, BCR-ABL, and EGF receptor oncogenes. Cancer Cell 10, 425–435 (2006)

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FURTHER READING

  1. Sharma, S. V, Fischbach, M. A., Haber, D. A. & Settleman, J. 'Oncogenic shock': explaining oncogene addiction through differential signal attenuation. Clin. Cancer Res. 12, 4392s–4395s (2006)

    Article  CAS  Google Scholar 

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Authors
  1. Jenny Bangham
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Bangham, J. Mysteries of addiction. Nat Rev Cancer 7, 4 (2007). https://doi.org/10.1038/nrc2058

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