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

(PHILADELPHIA) Scientists at Jeffersons Kimmel Cancer Center in Philadelphia have made an extraordinary advance in the understanding of the function of a gene previously shown to be part of an 11-gene signature that can predict which tumors will be aggressive and likely to spread. The gene, USP22, encodes an enzyme that appears to be crucial for controlling large scale changes in gene expression, one of the hallmarks of cancer cells.

As a result, USP22 immediately becomes a potential target for new anti-cancer drugs, says Steven McMahon, Ph.D., associate professor of Cancer Biology at Jefferson Medical College of Thomas Jefferson University, who led the work. And it solves a bit of a biological mystery.

Researchers knew that the gene USP22 was part of a group of 11 genes that are overexpressed in a variety of cancers and that overexpression of USP22 predicts which tumors can go on to spread elsewhere in the body. This group of genes is collectively called the cancer stem cell signature.

Such cancers that have those properties going on to be metastatic and resistant to therapy are referred to as having cancer stem cell-like features, Dr. McMahon explains. The genes in the signature are in a family of genes implicated as cancer stem cell markers. Many of them code for critical components of signaling pathways that are altered in cancer, making proteins that play roles in tumor growth. But unlike the other genes in the stem cell signature, the exact function of USP22 was not known.

Reporting January 18, 2008 in the journal Molecular Cell, Dr. McMahon and his co- workers have shown that not only is USP22 overexpressed in cancer cells, its enzymatic activity is necessary for some of the global changes in gene expression patterns that occur in these cells.

In one example, they looked at the relationship between MYC and USP22. MYC, which is among the most commonly overexpressed genes in cancer, e
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Contact: Steve Benowitz
steven.benowitz@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert

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