Cancer molecule is key to bowel cancer spread

Cancer Research UK scientists have uncovered a key function of the first ever molecule to be implicated in the development of cancer.

For many years scientists have known that the protein molecule – called Src – plays an important role in the progression and spread of bowel cancer, and other cancers, but until now no one knew what it actually did.

But a new study in the prestigious Nature Cell Biology journal¹ has revealed the mechanism for the molecule’s effects.

Src is involved in loosening the structure of tissues surrounding a tumour, opening the way for cancer cells to spread around the body. Scientists believe that developing drugs to block its action could prevent cancer from spreading.

Cells in healthy tissues are bound together by a number of molecules that work as a set of scaffolding. During the development of cancer the scaffolding breaks down and tissues become loose and disorganised.

Src seems to play a key role in this process. The molecule is vital for maintaining the flexibility of healthy tissues and making sure there’s plenty of space for future growth, but during the development of cancer it becomes over-active and begins to disrupt a tissue’s normal structure.

Team leader Professor Margaret Frame, based at Glasgow’s Beatson Institute, comments: “We were pretty sure that Src played an important role in bowel cancer, but untangling the precise nature of that role has taken a long time.

“We’ve now found that the molecule triggers several different chemical signals, affecting cells in a variety of ways. Designing drugs to intercept these signals could be an important way of preventing bowel cancer from spreading.”

Prof Frame and her colleagues found that Src sends out instructions for the removal of a molecule called E-cadherin from the surface of cells. E-cadherin is a vital component of the scaffolding that holds cells together and without it a tissue’s structure becomes disrupted.

Src appears to work with another set of molecules – called integrins – to form a new and much looser type of tissue structure that helps bowel cancer cells to move and spread.

Prof Frame adds: “Improving our understanding of how cancer spreads should help in the development of drugs to block the process. If we could confine cancer cells to the original tumour it would give surgery a much greater chance of success and reduce the risk of the disease reappearing in other parts of the body.”

When detected early bowel cancer is often curable, since most of the cancer cells remain within the original tumour, where they can be removed by surgery. But over time, cells start to move away from the tumour into the bloodstream and lymphatic system, which act as highways to the rest of the body. Once bowel cancer has spread, the chances of successful treatment are much lower.

Dr Richard Sullivan, Cancer Research UK’s Head of Clinical Programmes, says: “The key to successfully treating bowel cancer is to prevent the disease from spreading. Giving patients drugs to restore structure and order to tissues affected by cancer could be an important way of achieving this.”

ENDS