Skin cancer: Dr Chris outlines the signs of a melanoma

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A team from the The Institute of Cancer Research (ICR) in London has identified a nerve cell gene that enables melanoma – a type of skin cancer – cells to branch out and “invade” new tissues. They discovered this gene allows the cancerous cells to create “molecular drills” that then break through tissues and enable the spread. It is thought blocking this gene could ultimately stop the spread of cancer in the body.

As part of the research the scientists grew cells in a bioengineered 3D cell matrix and depleted hundreds of genes one at a time.

Using robotic microscopy and image analysis, they identified which genes were important for cancer cell shape.

It showed that depleting a specific gene called ARHGEF9 successfully destabilised the molecular drills on the cancerous cells.

This meant they were no longer able to attach to and punch holes through surrounding cells, and their ability to change shape was also reduced.

Professor of cancer morphodynamics at the institute, Professor Chris Bakal, explained: “Our work shows that melanoma cells borrow use of ARHGEF9 from nerve cells to change shape, branch out and invade new tissues.

“It’s incredibly important that we understand how cancer cells change their shape to become more aggressive and invasive.

“When cancers metastasise, they become much harder to treat.

“We’re working to better understand how cancer cells change shape and invade new tissues, so that one day we can find treatments that stop it.

“Our next step will be to look at the broader impacts of blocking ARHGEF9 to explore whether it could be suitable to target it with a drug to stop the gene from helping the cancer to spread.”

There are more than 16,000 new cases of melanoma in the UK each year, and cases continue to rise, with rates doubling since the early 1990s.

When melanoma cancer is diagnosed in its earliest stages, it can usually be effectively treated with surgery but it becomes much more difficult to treat as it becomes more aggressive, starts to move through tissues, and spreads to other parts of the body.

Professor Clare Isacke, dean of academic and research affairs at the ICR added: “The majority of cancer deaths occur because cancer has spread from the original tumour to other parts of the body, making the disease much harder to treat effectively.

“This research has made a fundamental discovery about how melanoma cells manipulate their shape to become invasive – the first step towards metastasis.

“Although it is early research, and more work needs to be done, by understanding more about how skin cancer spreads, we could open up new avenues for developing treatments which stop cancer in its tracks.”

ARHGEF9 usually plays a role in setting up connections between nerves during the development of the nervous system.

When ARHGEF9 is not working properly in the nervous system it can lead to epilepsy, and neurodevelopmental disorders like hyperactivity, anxiety, and autism-like traits.

The researchers say the gene is likely to be involved in the growth and spread of other cancer types – particularly neuroblastoma, a type of cancer that stems from nerve tissue and mostly affects children.

The most common sign of melanoma is the appearance of a new mole or a change in an existing mole – usually on the back in men and the legs in women.

In most cases, melanomas have an unusual shape and present as more than one colour.The mole may also be larger than normal and can bleed or be itchy.

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