P-Rex 1

Protein linked to spread of skin cancer

Tuesday 22 November 2011

An international team of researchers working together on both sides of the Atlantic have pinpointed a protein, called P-Rex1, that seems to play a key role in the spread of malignant melanoma – the most deadly form of skin cancer, according to a paper in Nature Communications.

The team, led by researchers from the Cancer Research UK-fundedBeatson Institute of Cancer Research in Glasgow, were studying cells called melanoblasts – highly mobile cells involved in the early development of the skin.

Researchers believe that the way melanoblasts move around body tissues very similar to how melanoma cells spread. The major cause of death from melanoma is due to it spreading, or metastasising, from the initial tumour.

The discovery came when the team noticed that mice which lacked the gene that which makes the P-Rex1 protein, had skin cancers that did not spread.

Armed with this knowledge, the research team then tested human melanoma cells and tumour tissue and discovered raised levels of P-Rex1, suggesting that the protein was involved in the movement of the cells.

The discovery will give researchers a better understanding of how the cells work, which in turn enables them to better select a target for developing new treatments.

Researcher Channing Der, a member of the team based at the Lineberger Comprehensive Cancer Center the US, said: "We know that mutations in a gene called BRAF are important for the development of melanoma and several years ago we published a collaborative paper listing 82 proteins that seem to be affected by this genetic pathway. From that list, we focused on P-Rex1."

The BRAF gene was discovered to be involved in melanoma by Cancer Research UK scientists, and this year a drug – vemurafenib – was developed that targets melanomas in which the BRAF gene is defective. This is thought to be the case for around 80 per cent of patients.

The discovery that P-Rex1 is 'downstream' of BRAF – in other words, signals coming from BRAF need to 'pass through' P-Rex1 – is significant because it suggests that drugs that target P-Rex1 could – in theory – help the 20 per cent of people with melanoma whose cancer doesn't have a faulty BRAF gene.

Nell Barrie, senior science information manager at Cancer Research UK, said: "Cancer is difficult to treat once it has spread, and research that helps us to understand how cancer cells travel around the body is helping scientists to target this process with new drugs. Studies like this give us more ammunition against melanoma and other types of cancer, but it's important to remember that it can take years to turn a discovery in the lab into a treatment for patients."

Copyright Press Association 2011