Seamus Martin and colleagues, Trinity College Dublin, Ireland, have discovered how autophagy – literally ‘self-eating’ – plays an important role in preventing the development of cancer. The protein, Noxa, was shown to have an unexpected role in triggering the self-eating process that leads early-stage cancer cells to self-destruct before they can develop into cancer.
Autophagy normally only occurs when cells experience periods of starvation, however, mutations in the Ras gene lead to excessive autophagy. The Ras gene is involved in approximately 30 % of human cancers and mutant Ras was found to promote autophagy by increasing the production of Noxa.
Members of the Bcl-2 gene family were shown to override this process, deactivating autophagy, leading to survival of cancerous cells. This suggests that drugs targeting Bcl-2 might reactivate the natural self-destruction pathway and lead to new treatments for cancer.
Image: (c) Heulwen Price/Wiley-VCH
- Oncogenic Ras-Induced Expression of Noxa and Beclin-1 Promotes Autophagic Cell Death and Limits Clonogenic Survival
M. Elgendy, C. Sheridan, G. Brumatti, S. J. Martin,
Molecular Cell 2011.