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 Tracing the evolution of vision
23.08.2019 | University of Göttingen

nachricht Caffeine does not influence stingless bees
23.08.2019 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Hamburg and Kiel researchers observe spontaneous occurrence of skyrmions in atomically thin cobalt films

Since their experimental discovery, magnetic skyrmions - tiny magnetic knots - have moved into the focus of research. Scientists from Hamburg and Kiel have now been able to show that individual magnetic skyrmions with a diameter of only a few nanometres can be stabilised in magnetic metal films even without an external magnetic field. They report on their discovery in the journal Nature Communications.

The existence of magnetic skyrmions as particle-like objects was predicted 30 years ago by theoretical physicists, but could only be proven experimentally in...

Im Focus: Physicists create world's smallest engine

Theoretical physicists at Trinity College Dublin are among an international collaboration that has built the world's smallest engine - which, as a single calcium ion, is approximately ten billion times smaller than a car engine.

Work performed by Professor John Goold's QuSys group in Trinity's School of Physics describes the science behind this tiny motor.

Im Focus: Quantum computers to become portable

Together with the University of Innsbruck, the ETH Zurich and Interactive Fully Electrical Vehicles SRL, Infineon Austria is researching specific questions on the commercial use of quantum computers. With new innovations in design and manufacturing, the partners from universities and industry want to develop affordable components for quantum computers.

Ion traps have proven to be a very successful technology for the control and manipulation of quantum particles. Today, they form the heart of the first...

Im Focus: Towards an 'orrery' for quantum gauge theory

Experimental progress towards engineering quantized gauge fields coupled to ultracold matter promises a versatile platform to tackle problems ranging from condensed-matter to high-energy physics

The interaction between fields and matter is a recurring theme throughout physics. Classical cases such as the trajectories of one celestial body moving in the...

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

Tracing the evolution of vision

23.08.2019 | Life Sciences

Software for diagnostics and fail-safe operation of robots developed at FEFU

23.08.2019 | Information Technology

Structure of protein nano turbine revealed

23.08.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>