Scientists from The Institute of Cancer Research (ICR) showed that in human cancer cells and mice, a gene called BRAF – which is damaged in about half of all skin cancer cases – triggers a cell signalling pathway that ultimately ‘blocks the instructions’ from a second gene called PDE5A.
In healthy cells PDE5A acts as a brake to stop cell movement. But in cancer cells, BRAF turns PDE5A’s signals off, removing its ability to block cancer spread.
By blocking the activity of PDE5A, BRAF drives skin cancer cells to invade new tissues and spread further around the body, converting skin cancer into a more aggressive disease.
The team showed that when faulty BRAF blocked PDE5A, the skin cancer cells spread more easily to the lungs.
Lead study author, Professor Richard Marais, said: “This research further puts the focus on BRAF as an important target for therapy to prevent the spread of skin cancer.
“Our findings support recent studies into experimental BRAF-targeting drugs, which are showing great promise in patients with melanoma cells with a damaged BRAF gene, but not in patients whose melanomas do not have this alteration. This highlights the importance of personalising medicine to achieve effective treatments for cancer.”
Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “These new findings reveal more of the complex web of signals that drive the development of tumours that have the ability to grow, survive and spread to new locations.
“Melanoma is the most dangerous form of skin cancer and more than 2,000 people die from the disease each year. Even more worrying is the fact that rates of melanoma are rising.
“There are definite signs when a mole is suspicious and should be seen by a doctor. If you have a mole that is getting bigger, changing shape or colour, is itchy or painful, bleeding or inflamed you should go to the doctor straight away.”
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Arozarena, I., et al. Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A (2011) Cancer Cell