Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson scientists uncover role of cancer stem cell marker: controlling gene expression

22.01.2008
Scientists at Jefferson’s 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.

... more about:
»Expression »McMahon »Myc »Signature »Stem »USP22

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.

“We’ve 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.”

Steve Benowitz | EurekAlert!
Further information:
http://www.jefferson.edu

Further reports about: Expression McMahon Myc Signature Stem USP22

More articles from Life Sciences:

nachricht Overlooked molecular machine in cell nucleus may hold key to treating aggressive leukemia
23.04.2019 | Cincinnati Children's Hospital Medical Center

nachricht Bacteria use their enemy -- phage -- for 'self-recognition'
23.04.2019 | Chinese Academy of Sciences Headquarters

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

Marine Skin dives deeper for better monitoring

23.04.2019 | Information Technology

Geomagnetic jerks finally reproduced and explained

23.04.2019 | Earth Sciences

Overlooked molecular machine in cell nucleus may hold key to treating aggressive leukemia

23.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>