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Natural anti-viral enzyme helps keep cancer cells alive, researchers find

DALLAS Oct. 6, 2006 -- A molecule that cells normally use to fight viruses is also involved in keeping cancer cells alive, researchers at UT Southwestern Medical Center have discovered.

The anti-viral molecule, called TBK-1, was found to be essential for cancer cells to live, so blocking it might point to a treatment for fighting cancer, the researchers report in today's issue of Cell.

"We got the surprise that this mechanism is involved in cancer cell survival, even though it's normally involved in immune response," said Dr. Michael White, associate professor of cell biology. "We found something a little bit different an Achilles' heel of cancer cells that's apparently broadly conserved among many types of solid tumors."

Using cultured human cells, the researchers set out to study enzymes known to be involved in keeping cancer cells alive and proliferating. They soon narrowed the focus to one called RalB. This molecule is part of the Ras family of enzymes, which are mutated in 30 percent of all cancers and in 90 percent of pancreatic cancers.

The UT Southwestern scientists knew that RalB interacts with a protein complex called the exocyst, which helps small secretory packets in cells fuse to the cell membrane. The team isolated this complex, then chemically analyzed the proteins attached to it.

One protein they found on the exocyst, TBK-1, is known to be involved in cells' anti-viral response.

"There was nothing known about that mechanism to suggest how TBK-1 could drive cancer cell survival," Dr. White said.

The researchers found that TBK-1 is turned off in healthy cells unless the immune response is stimulated but was always active in the cancerous cells they studied. When they blocked the function of TBK-1 in both the cancerous and healthy cells, cancer cells died while healthy cells survived.

A German research team has studied clinical samples of tumors and found elevated levels of TBK-1, Dr. White said.

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Contact: Aline McKenzie
aline.mckenzie@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
5-Oct-2006


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