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Newly-described route to cancer solves a mystery in lung cancer

HOUSTON - Researchers at The University of Texas M. D. Anderson Cancer Center are describing an entirely new way by which cells can become cancerous. And they say their finding provides an answer to a mystery in lung and other cancers: why a potent tumor suppressor gene called FUS1 functions as it should, yet none of the protein it produces can be found anywhere in a cancer cell.

In the May issue of Cancer Research, Advances in Brief, the investigators report that protective proteins made by FUS1 are, in fact, normal, but that a critical modification that should take place after they are produced does not - and this renders the proteins inert.

Specifically, they found the defect is in a common cell process known as "myristoylation" that occurs when chains of fatty acids hook on to newly-minted proteins, which allows them to stick to the oily surface of the cell membrane.

In this case, the fatty acids don't attach on to the FUS1 protein, for reasons that are not understood, and the non-functional proteins are quickly broken apart inside the cell. Without FUS1 protein, cells cannot self destruct if damaged, thus cancer development can proceed unchecked.

This is the first time that myristoylation has been fingered as a potential root cause of cancer, say the researchers.

"Most genetic mechanisms for causing cancer include mutations that make gene products overactive or inactive. That's not the case here," says the study's senior author, Lin Ji, Ph.D., assistant professor in the Department of Thoracic & Cardiovascular Surgery Research. "This is a novel mechanism, a completely new way of disabling a tumor suppressor protein."

Loss of functional FUS1 "is certainly one of the earliest changes that occurs in lung cancer, and it likely happens in other cancers, such as breast and kidney, where the gene is known to be a target for inactivation," says co-author Jack Roth, M.D. chair of the Department of Thoracic & Cardiovascula
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Contact: Julie Penne
jpenne@mdanderson.org
713-792-0662
University of Texas M. D. Anderson Cancer Center
5-May-2004


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