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Stopping cancer in its tracks

Researchers know cancer cells have to take on different shapes so they can metastasise, or move around the body. For example, in the blood and in soft tissues, cancer cells adopt a rounded shape. But when travelling across bone and other hard tissues, they become elongated. It’s like us getting across ice and water – we need different pieces of equipment to do this. Without the ability to assume these shapes, cancer cells cannot spread.

Until recently, we knew hardly anything about the mechanisms behind this shape switch. But Dr Chris Bakal and his team have pinpointed a set of genes that allows melanoma cells to change rapidly between two shapes in order to escape from the skin and spread around the body. Researchers saw that by switching off a gene called PTEN, they could increase the number of elongated cells, and this appears to help the disease move through tissues. PTEN is an important tumour suppressor – a gene that appears to stop healthy cells from becoming cancerous – and it is switched off in around one in eight patients with melanoma and in almost half of those who carry a mutation in another cancer gene called BRAF. Scientists think one way melanoma cells can metastasise is by losing their PTEN function, increasing their shape-shifting ability and in turn enabling them to move to many different tissues within the body.

These early findings could pave the way for scientists to develop desperately needed drugs for malignant melanoma which kills more than 2,200 people every year. Melanoma spreads very easily to other areas like the liver, lungs or brain, and once it has spread it becomes very difficult to treat. Surgery or radiotherapy may eradicate tumours at their site of origin, but current treatment options are rarely able to cure cancer once it has spread. Crucially, by understanding how cells shape shift, we might find a way to control metastatic cancer through drugs or other therapies.

Melanoma cells (Dr Chris Bakal / the ICR)
Zheng Yin, Amine Sadok, Heba Sailem, Afshan McCarthy, Xiaofeng Xia, Fuhai Li, Mar Arias Garcia, Louise Evans, Alexis R. Barr, Norbert Perrimon, Christopher J. Marshall, Stephen T. C. Wong & Chris Bakal. A screen for morphological complexity identifies regulators of switch-like transitions between discrete cell shapesNature Cell Biology (2013) doi:10.1038/ncb2764


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