A common, yet previously undistinguished protein, which is elevated in many late-stage cancers, may play a strategic role in tumour growth through a non-conventional pathway, researchers at the Indiana University School of Medicine report in the Proceedings of the National Academy of Sciences. The protein, Mdm2, an oncogene, has long been thought to play a major role in regulating the effectiveness of the tumour suppressor p53, largely through p53’s destruction. New research shows that Mdm2 plays an active role in making p53 ineffective without eradicating it from the cell.
The team state the current study provides new evidence on the mechanism through an unrealized pathway that can spur on cell growth and metastasis.
The central dogma for almost 20 years has been that the main function of Mdm2 is to bind to a protein and flag it to be destroyed. Everyone thought that Mdm2 research had hit a plateau from these findings.
In research published in the Journal of Clinical Investigation in 2010 the team identified a critical pathway that stimulates the production of Mdm2 causing an increase in the level of protein that binds to p53, the most common tumour suppressor, as well as other tumour suppressors, and extinguishes tumour suppression activity. Since elevated levels of Mdm2 are found in late-stage cancers, the researchers began to test what elevated Mdm2 was doing in the cells.
The tumour uses Mdm2 to either destroy p53, or put p53 in suspended animation. The suspended animation is the revelation that the lab discovered in the current study. In either case this provides a growth advantage, but also requires different therapeutic approaches to turn off Mdm2 for activation of p53 to halt tumour growth.
The team explain that what is exciting is finding alternate or novel pathways for Mdm2, changing its perceived manner of blocking p53 as a tumour suppressor. This research will provide additional therapeutic options.
Source: IUSM Newsroom