The linker histone H1.0 generates epigenetic and functional intratumor heterogeneity.
Scientists have revealed how a genetic switch involved in the packaging of DNA may be key to a cancer cell’s ability to keep growing.The Francis Crick Institute researchers found that production of a protein called H1.0 was frequently switched off in many cancer types and that reactivating this protein halted tumour growth. Studying cancer cells lacking H1.0, they found that DNA becomes uncoiled at key points, activating a series of genes that stall the cell in an ‘immature’ state. This allows the cells to carry on dividing and expanding the tumour.
But as the tumour grows H1.0 can spontaneously become switched back on in some cells. The researchers traced this back to a region of the DNA that acts as the control switch for H1.0 production. With H1.0 back up and running, the genes needed for the cell to keep on dividing are shut down again, returning it to a normal finite lifespan.
The Crick team are now searching for drugs that could speed up this process by kick-starting H1.0 production throughout the tumour. This could potentially provide an effective way of halting tumour growth across a range of tumour types.
Dr Paola Scaffidi, a research group leader at the Crick and part-funded by Cancer Research UK, said: “This research opens up the possibility of one day turning harmful tumours into benign ones by reverting cancer cells back to a finite lifespan, which would eventually cause the tumour to stop growing. Importantly, we’ve shown that patients whose tumours had low levels of H1.0 tend to do worse and that this was apparent across a range of cancers.
“We now know where to start looking for drugs that work by revoking cancer cells’ immortality, rather than just killing them off.”
Eleanor Barrie, Cancer Research UK’s senior science information manager, said: “Drugs targeting the way cancer cells disrupt gene activity by altering how DNA is packaged are an exciting new avenue of research, with some treatments entering trials for leukemia patients. This intriguing study is one of the first to suggest how this approach could work in solid tumours and adds another layer to our understanding of the different types of cells that make up a tumour.” http://www.cancerresearchuk.org/about-us/cancer-news/press-release/2016-09-29-genetic-switch-for-cancer-cells-immortality-revealed
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