Genes help shape-shifting skin cancer cells to spread

Researchers have identified a set of genes that regulate the ability of melanoma cells, a type of cancer cell, to change rapidly between two shapes to escape from the skin and spread around the body.

This new research – funded by the Wellcome Trust, Cancer Research UK and the US National Institutes of Health – could pave the way for scientists to develop desperately needed drugs for malignant melanoma, the deadliest form of skin cancer, which kills more than 2,200 people every year.

The most dangerous aspect of melanoma is its ability to spread, or become malignant, to other parts of the body in the later stages of disease. This most often includes the liver, lungs and brain.

Dr Chris Bakal, a Wellcome Trust research fellow at the Institute of Cancer Research, London, explains: "We already knew that metastatic melanoma cells, or cells that are able to spread through the body, have to be able to adopt different shapes so that they can squeeze their way between healthy cells and move around the body.

"The cells have to become rounded to travel through the bloodstream or invade soft tissues such as the brain, but they take on an elongated shape to travel through harder tissues like bone. But until now, we knew hardly anything about how the cells assume either of these shapes and how they switch between the two."

To investigate this, researchers at the Institute of Cancer Research, London, and Weill Cornell Medical College in Houston started out by looking at fruit fly cells. They found that under normal conditions, the fruit fly cells grew in five different shapes. By switching off specific genes, they were able to change the mix of shapes among the fruit fly cells and identify several different genes that control a cell's shape-shifting ability.

When they looked in human melanoma cells, they found that the human versions of these genes had a similar effect. In particular, they noted that switching off a gene called PTEN increased the proportion of cells that were elongated rather than rounded.

PTEN is a gene that is also involved in stopping healthy cells from becoming cancer cells, a so-called 'tumour suppressor' gene. This particular gene is switched off in around 1 in 8 melanoma patients and in almost half of melanoma patients who carry a mutation in another cancer gene called BRAF.

"We think that metastatic melanoma cells lose their PTEN function so that they can increase their shape-shifting ability, which in turn enables them to move to many different tissues within the body. It's early days, but taken together our findings offer new opportunities to develop drugs to try and stop the spread of melanoma," Dr Bakal added.

Dr Julie Sharp, Senior Science Communications Manager at Cancer Research UK, said: "This is still early research, but it gives us a better grasp of the way cancer cells behave in the body. By mimicking these conditions, our researchers are learning more about melanoma and bringing us closer to beating it.

"Melanoma is the most deadly form of skin cancer because it spreads very easily. This makes it harder to treat and is why early diagnosis is so important – to catch the disease before it spreads to other areas."