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Drug targets cell ‘velcro’to stop spreading of cancer

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CANCER RESEARCH UK scientists in Scotland have identified potential drug targets to prevent cancer cells breaking away from tumours and spreading round the body, according to research presented at the NCRI Cancer Conference in Birmingham today.

Scientists based at Cancer Research UK’s Beatson Institute for Cancer Research in Glasgow studied cancer cells and mice to better understand the role of integrins – the body’s ‘velcro’ which anchors healthy and cancer cells – and stops the spread of cancer cells round the body.

Integrin molecules are located on the surface of cells and normally ‘grip’ healthy cells, anchoring them in the appropriate place to form tissues and organs. This prevents cells breaking away and travelling to other parts of the body where they might cause harm.

The team found that faults in an important protein called p53 can interfere with the way integrins are distributed across the cells’ surface – so instead of the cells being tethered, as happens in healthy tissues, they drift throughout the body.

p53 has been called the guardian of the genome because of its ability to control cell growth and division. It does not work properly in half of cancers and is thought to be the reason many cancers develop.

Faulty p53 switches on a cell signalling system called the Rab-coupling protein (RCP) pathway. This interferes with the normal delivery route of integrins to the cell’s surface. It causes a delivery mistake and the integrins are sent to the wrong part of the cell. The sticky integrins then work differently, causing the cells to move around in the body rather than being anchored in their ‘home’ tissue or organ.

Professor Jim Norman from Cancer Research UK’s Beatson Institute, who is presenting this work at the NCRI Cancer Conference today, said: “This is exciting research. These results could lead to the development of new potential targets for future drugs to stop cancer spread.

“While it maybe some time before such drugs are available, there are clinical trials already in progress to test whether drugs that block integrins can be used to treat cancer – but now we know p53 plays a key role in changing the way integrin behaves to drive cancer spread.”

He added: “Further trials testing therapies using drugs which block sticky integrin, combined with studies into the role of mutant p53, may enable scientists to design drugs that target cancer cells better whilst leaving healthy cells unharmed.”

ENDS

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Vousden, K. et al Mutant p53 regulates invasion via integrins and EGFR NCRI Cancer Conference5 October 2009