A genetic switch involved in the packaging of DNA may be key to
a cancer cell's ability to keep growing, scientists at the Francis
Crick Institute have found.
The Crick team, part-funded by Cancer Research UK, 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 leukaemia
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."
The paper, 'The linker histone H1.0 generates epigenetic
and functional intratumour heterogeneity', is published in the
journal Science.