Scientists discover genetic 'off switch' for series of cancers

Published on Monday 23 February 2009 22:50

SCIENTISTS have identified a cancer "master switch" that could open the door to revolutionary new treatments, research published today reveals.

Activating a specific gene common to fruit flies, mice and humans may allow cancer to be "switched off", researchers say.

The work has major implications for treating and curing cancers by snuffing out the root of tumour formation.

Last night, cancer charities welcomed the research into the disease, which is one of the top three killers in Scotland.

Each year, 289,000 people in the UK are diagnosed with cancer including 27,000 in Scotland – 74 a day.

The discovery outlined in two scientific papers today relates to eye tumours in flies and bowel cancers in mice and humans. But other "master switches" common to different species may exist for other cancers.

All belong to a gene family vital to "differentiation", the process by which cells acquire specialist roles in the body.

Cancer cells, by definition, have no function and are less differentiated than normal cells.

The new research, published in the online journal PLoS Biology, focuses on the Atoh1 gene in mice and humans and its fruit fly equivalent, Ato. Both belong to the "Atonal" group of genes, which are thought to be key controllers.

Scientists showed that Atoh1 suppressed bowel cancer in both mice and humans, while Ato prevented eye tumours developing in fruit flies.

Switching off the gene triggered the growth of cancers in flies, mice and humans. Mice lacking Atoh1 developed bowel cancer. The same was true with human patients.

Laboratory experiments showed that loss of Atoh1 not only led to the formation and growth of bowel cancer, but also Merkel cell carcinoma – a rare but deadly form of skin cancer.

Reactivating the gene in laboratory-grown cancer cells caused the tumours to stop dividing and die.

Separate teams of scientists led by Dr Wouter Bossuyt, of the VIB biotechnology institute and KU Leuven School of Medicine in Belgium, carried out the research.

The authors wrote: "We suggest that Ato/Atoh1 and similar genes are important brakes on malignant transformation."

Cells begin differentiating in the womb. During embryonic development, they repeatedly divide and become increasingly different from each other.

In an adult, almost every cell is highly specialised and assigned a particular job. Skin, liver, nerve and bone cells all look and behave differently.

Cancer reverses the process, causing cells to become less differentiated. Like the cells of the developing embryo, cancer cells also divide rapidly.

Atoh1 appears to switch on the last step in the specialisation of cells lining the intestine. Removing or deactivating it reverses differentiation, leading to cancer. Reactivating it engages the differentiation process again and suppresses tumour formation.

Dr Bossuyt and his colleagues raised the possibility of further "master switch" genes affecting other cancers.

There was already evidence that related genes might play a role in the early stages of breast cancer development, the scientists said.

Dr Joanna Owens, Cancer Research UK's science information manager, said: "This is an exciting addition to what we already know about the key molecular triggers for cancer formation. If we can understand more about these crucial events, we can find new ways to put the brakes on cancer."

A spokesman for Macmillan Cancer Support in Scotland said: "Early diagnosis and treatment of cancer is essential for improving survival rates and reducing anxiety and distress in patients, so news about any new potential treatment is always welcome.

"However, with two million people now living with or beyond cancer in the UK, support and access to information is also crucial."