Scottish scientists find keystone defence against cancer

Cancer Research UK

Cancer Research UK scientists in Scotland have uncovered a crucial safeguard that protects the body against cancer.

In a study1 published today, researchers in Dundee report that a keystone molecule called ARF seems to protect healthy cells by switching off sinister signals that might otherwise turn them cancerous.

Mimicking the action of the safeguard could be an exciting anti-cancer strategy, they believe, killing cancer cells outright or making them more sensitive to the effects of chemotherapy.

ARF is known to play an important role in protecting against cancer. Cancer Research UK scientists at the School of Life Sciences, University of Dundee, looked at whether the molecule could prevent some of the critical stages in the development of cancer.

They found that giving cancer cells ARF knocks out the action of a molecule called NF-kappaB, a key signal which in some circumstances can encourage the transition from healthy cells to cancer.

Blocking NF-kappaB prevents cells from responding to cancer-promoting messages telling them to grow, divide or spread around the body.

Dr Neil Perkins, leading the Cancer Research UK-funded team, says: "We've uncovered an important natural mechanism which protects healthy cells from cancer, but which we think occasionally malfunctions to allow some cancerous cells to slip through the net.

"Knowing how the safeguard works is an important advance, because it highlights a new and potentially valuable route to attack cancer cells."

Researchers believe that during the development of cancer, ARF may become inactivated, leaving NF-kappaB free to encourage the disease to progress. Knocking out NF-kappaB could be an effective treatment, since it might prevent cells from reacting to messages telling them to grow and spread.

And it may be of greatest use for making cancer cells more sensitive to the effects of existing types of chemotherapy, since it is known that NF-kappaB also plays an important role in protecting cancer cells from the effects of anti-cancer drugs.

In healthy tissue, NF-kappaB is usually only switched on in response to infection or cell damage, helping tissue to recover and keeping damaged cells alive. In cancer, its function becomes subverted and it uses these abilities to allow tumours to resist the cell-killing effects of chemotherapy.

Dr Richard Sullivan, Head of Clinical Programmes for Cancer Research UK, says: "Cancer is an incredibly complex group of diseases, so our research has to be innovative and wide-ranging if we are to find ways of tackling some of the more stubborn kinds.

"This study has suggested an intriguing new avenue of attack against cancer, which aims to exploit one of the body's own defence mechanisms to keep the disease at bay."

ENDS

  1. Molecular Cell12 (1): pp.15-25.

Note to Editors:

The new study adds to our knowledge of ARF, which was already known to be part of a system to control cell growth and division and to cull irreparably damaged cells. It works together with the 'guardian of the genome', p53, which was discovered by another Cancer Research UK scientist based in Dundee, Sir David Lane.