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Scientists find trigger to aggressive bowel cancer

18 November 2008

Scientists from the School of Biosciences have taken part in a collaborative study into one of the most common cancers in the UK, which has shown how bowel cancer can become aggressive.

The study, published in Nature Genetics, and developed with scientists at Cancer Research UK’s Beatson Institute in Glasgow, has found that a tumour suppressor protein called Pten is critical in stopping tumours from growing in mice. Importantly, they found that when Pten becomes faulty some of these tumours turn aggressive.

The team worked out that when Pten faults coincide with faults in another protein called APC, then a kinase protein called AKT stimulates tumours to become aggressive and they are then more likely to spread. They have identified AKT as a strong lead for drug development to target bowel cancer.

Previously scientists thought that faulty Pten was important in the early stages of bowel cancer initiation, but the researchers have found that the situation is far more complex, with faulty Pten a trigger that can act later on tumours to make them aggressive.

The team, led by Professor Alan Clarke, Cancer Research UK’s lead researcher at the School of Biosciences, showed that Pten slows the growth of tumours in mice following the activation of a molecular pathway called WNT. This pathway involves numerous proteins talking to each other to ultimately control cell division. WNT is already known to be the molecular pathway most commonly faulty in bowel tumours.

Professor Alan Clarke said: "These findings are really interesting. We now know that the protein kinase AKT is a real lead for drug development to target aggressive intestinal cancer, which is something we didn't properly appreciate before.

"We now have a model of how bowel cancer progresses. Previously scientists only had a very limited idea of how bowel tumours were believed to progress.

"This has given us a clearer picture of how bowel tumours actually grow and provides scientists with crucial information for drug design to slow down or stop the spread of the disease."

Cancer is caused by uncontrolled cell growth and division. Identifying the key proteins which control complicated molecular networks inside cells and what happens when these proteins become faulty, is fundamental to our understanding how cancer develops.

Dr Lesley Walker, Cancer Research UK’s director of cancer information, said:
"This is a really important piece of science. Bowel cancer is one of the most common diseases in the UK and it is much more difficult to treat when it is advanced, so we welcome any research that gives us opportunities for better treatment."

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