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New pathway identified for debilitating skin condition

Scientists have discovered that a type of signal within tumour cells is critical to the development of a rare and debilitating inherited skin condition.

Researchers at The Institute of Cancer Research, London, found that a signalling process called Notch signalling was turned up to higher than normal levels in the cells of people with a disease called cylindromatosis – in which multiple skin tumours form on the face.

People with cylindromatosis have inherited a faulty version of the CYLD gene, meaning their cells lack a working CYLD protein. The new study, published in Oncotarget, found that Notch signalling was turned up in tumour cells lacking CYLD – and that this could be the main driver of tumour growth.

Professor Alan Ashworth, former Chief Executive of the ICR originally carried out work highlighting the tumour-suppressing qualities of CYLD in cylindromatosis. At the time, these tumours were thought to be driven by cell signalling through the NF-κB pathway.

But the new research, a collaboration between Professor Ashworth’s lab at the ICR and Dr Neil Rajan at the University of Newcastle, suggests that another signalling process is involved – Notch signalling.

Researchers observed an increase in Notch signalling in cells which lacked the protein CYLD. Further analysis showed that CYLD is able to ‘turn off’ one of the proteins involved in Notch signalling – a protein known as MIB2. In turn, MIB2 controls the function of CYLD, and the process regulates itself.

Dr Chris Lord, co-author of the paper and a team leader at the ICR, said: “Our results suggest that Notch signalling might also underlie the behaviour of cells in cylindromatosis.  By carrying out this type of work with our collaborators in Newcastle, we are aiming to get a better understanding of the biology of this disease. We hope that ultimately this work, along with the efforts of others, could give us an insight into how we might better manage cylindromatosis.”


rare cancers
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