Scientists find a trigger to aggressive bowel cancer

Cancer Research UK

CANCER RESEARCH UK scientists have shown how bowel cancer can become aggressive, according to research published in Nature Genetics* today (Sunday).

The researchers, based in the Cardiff School of Biosciences, Cardiff University and at Cancer Research UK's Beatson Institute in Glasgow 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 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 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.

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.

Professor Alan Clarke, Cancer Research UK's lead researcher at the Cardiff School of Biosciences, 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."

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."

ENDS

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Notes to Editor

*Victoria Marsh et al. Epithelial Pten is dispensible for intestinal homeostasis but suppresses adenoma development and progression after Apc mutation. Nature Genetics, advance online publication, Sunday 16 November.

Cardiff University

Cardiff University is recognised in independent government assessments as one of Britain’s leading teaching and research universities. 2008 marks the 125th anniversary of Cardiff University having been founded by Royal Charter in 1883. Today the University combines impressive modern facilities and a dynamic approach to teaching and research. The University’s breadth of expertise in research and research-led teaching encompasses: the humanities; the natural, physical, health, life and social sciences; engineering and technology; preparation for a wide range of professions; and a longstanding commitment to lifelong learning. Cardiff is a member of the Russell Group of the UK’s leading research universities. Visit the University website at: www.cardiff.ac.uk

Cardiff School of Biosciences

The Cardiff School of Biosciences addresses the major biological questions which face health and life scientists. The major research areas of the School are: biodiversity and ecology, connective tissue biology, environmental biochemistry and microbiology, mammalian genetics, molecular enzymology and entomology, and neuroscience cell biology. The School also houses the Common Cold Centre, the world’s only centre dedicated to researching and testing new medicines for treatment of the symptoms of flu and the common cold. The School achieved a one hundred per cent success in the national, independent assessment of university teaching quality. The top ‘excellent’ grade was awarded to Pure and Applied Biology, Biochemistry, Anatomy and Physiology, and to the first and second year pre-clinical training for doctors and dentists.

The symptoms of colorectal (bowel) cancer

Bleeding from the rectum or blood in your stools; a change in normal bowel habits towards diarrhoea or looser stools that lasts longer than six weeks; a lump that your doctor can feel in the right side of your abdomen, or in your rectum; a straining feeling in the rectum; losing weight; pain in your abdomen or rectum; anaemia (a low level of red blood cells); because bowel tumours can bleed at times, cancer of the bowel often causes a shortage of red blood cells, called anaemia. It can lead to tiredness and sometimes breathlessness.

Sometimes cancer of the bowel can cause a blockage.

The symptoms of this are: Griping pains in the abdomen; feeling bloated;constipation and being sick.

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