Navigation Links
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, encodes 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.


'/>"/>

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

Related medicine news :

1. Time Critical Diagnosis Task Force Convenes in Jefferson City
2. Jefferson scientists find protein helps pancreatic cancer cells evade immune system and spread
3. Jefferson scientists find protein potential drug target for treatment-resistant prostate cancer
4. Jefferson vascular surgeon heads national trial for torn aorta repair
5. Jefferson neuroscientists find early lead exposure impedes recovery from brain injury
6. Jefferson scientists see breast cancer gene activity from outside the body
7. Jefferson scientists uncover key pathway, potential drug targets in autoinflammatory disease
8. Jefferson neuroscientists show anti-inflammation molecule helps fight MS-like disease
9. Jefferson researchers show chemotherapy and radiation together extend lung cancer patients lives
10. Jefferson researchers find stem cells in degenerating spinal discs, potential for repair
11. Jefferson oncologists show focused radiation is effective as surgery against nerve tumor
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/25/2016)... ... June 25, 2016 , ... "With 30 hand-drawn hand ... project," said Christina Austin - CEO of Pixel Film Studios. , ProHand Cartoon’s ... within Final Cut Pro X . Simply select a ProHand generator and drag ...
(Date:6/25/2016)... Oklahoma (PRWEB) , ... June 25, 2016 , ... ... both athletes and non-athletes recover from injury. Recently, he has implemented orthobiologic procedures ... Oklahoma City area —Johnson is one of the first doctors to perform the ...
(Date:6/24/2016)... ... 24, 2016 , ... A recent article published June 14 on ... article goes on to state that individuals are now more comfortable seeking to undergo ... such as calf and cheek reduction. The Los Angeles area medical group, Beverly Hills ...
(Date:6/24/2016)... ... ... a crisis. Her son James, eight, was out of control. Prone to extreme mood shifts ... upset him, he couldn’t control his emotions,” remembers Marcy. “If there was a knife ... and say he was going to kill them. If we were driving on the ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... now offering micro-osteoperforation for accelerated orthodontic treatment. Dr. Cheng has extensive experience with ... Damon brackets , AcceleDent, and accelerated osteogenic orthodontics. , Micro-osteoperforation is a ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... LEXINGTON, Mass. , June 24, 2016   ... specialty pharmaceutical company developing innovative inhaled drugs, announced today ... when Russell Investments reconstituted its comprehensive set ... 2016. "This is an important milestone for ... "It will increase shareholder awareness of our progress in ...
(Date:6/23/2016)... Research and Markets has announced the addition of the ... report to their offering. ... failure, it replaces the function of kidneys by removing the ... the treatment helps to keep the patient body,s electrolytes such ... Increasing number of ESRD patients & substantial healthcare expenditure on ...
(Date:6/23/2016)... , June 23, 2016 Roche (SIX: ... 510(k) clearance for its Elecsys BRAHMS PCT (procalcitonin) assay ... sepsis or septic shock. With this clearance, Roche is ... a fully integrated solution for sepsis risk assessment and ... with bacterial infection and PCT levels in blood can ...
Breaking Medicine Technology: