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Jefferson scientists uncover role of cancer stem cell marker: controlling gene expression
Date:1/17/2008

ncodes a protein that controls the expression of thousands of other genes. The scientists showed that USP22 is a critical partner of MYC and that by depleting cells of USP22, they could prevent MYC from working properly, stopping it from inducing the invasive growth of cancer cells.

Weve shown that the MYC pathway is among the transcriptional programs that require USP22, Dr. McMahon says. Identifying USP22 as a global transcription regulator helps explain why it is part of this aggressive stem cell signature.

Dr. McMahon and his group determined how USP22 works at the biochemical level and found that it is part of a large complex of proteins called human SAGA. According to Dr. McMahon, these proteins are responsible for turning on genes, helping them get expressed more efficiently. This suggests that the genes that are turned on by the USP22 complex are important for altering cancerous cells in such ways that they become more aggressive and metastatic.

Discovering the identity of the 11-gene signature that predicts aggressive, therapy- resistant tumors a few years ago was certainly a critical advance in terms of the ability to diagnose and stratify patients, Dr. McMahon says. Since USP22 is an enzyme, the type of protein that is easiest to target with drugs, our new findings may help extend these earlier discoveries to the point where therapeutics can be developed. There are already drugs being used in cancer patients that attack other enzymes in this pathway, and there are companies interested in extending this to find USP22 inhibitors.


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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert

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