Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Potential ’weak link’ between virus and liver cancer discovered

22.07.2005


Researchers at The University of Texas M. D. Anderson Cancer Center have uncovered a crucial molecular link between a viral infection and development of a common and fatal form of liver cancer. In the process, they have identified a possible way to treat this disease as well as a number of other cancers.



In findings reported in the journal Molecular Cell, the researchers traced the pathway by which the hepatitis B virus (HBV) leads to development of hepatocellular carcinoma (HCC) and found that it "turns off" an enzyme known as GSK-3ß, which acts to suppress tumor formation as well as inhibit the spread of cancer.

GSK-3ß could prove to be the Achilles heel for liver cancer and other tumors - including breast, colon, kidney and stomach - that use a similar "pathway" to cancer development, the researchers say.


"This study identified a novel mechanism for how hepatitis B primes liver cells to turn cancerous, and what we found has potential relevance for other cancers as well," says the study’s lead author Mien-Chie Hung, Ph.D., professor and chair of the Department of Molecular and Cellular Oncology. Hung collaborated with a team of researchers that included scientists from Baylor College of Medicine in Houston, Germany, Taiwan and China.

Infection from HBV is widespread throughout the world, especially in developing nations, and is considered by the World Health Organization (WHO) to be a serious global health problem. The virus, transmitted by blood or body fluids, is up to 100 times more infectious than HIV (human immunodeficiency virus).

Of the 2 billion people who have been infected with HBV, more than 350 million have chronic, or lifelong, infections that put them at high risk of death from cirrhosis of the liver and liver cancer, according to WHO. These diseases kill about one million people worldwide each year.

"HCC accounts for up to 90 percent of all liver cancers, and individuals who carry the hepatitis B virus have a greater than 100-fold increased relative risk of developing HCC," Hung says. "Many researchers have been working to understand how the virus causes this cancer so that potential treatments can be designed."

Scientists have long linked development of HBV to HCC, the most common form of liver cancer. They also believe that this cancer is due to activation of a signaling pathway that includes a protein known as beta catenin. When this protein functions normally, it sits on the outside surface of a cell and helps the cell stick to others like it in a tissue, but when it is found inside the cell’s cytoplasm or nucleus, it works to turn on genes involved in cancer development. In the study, 50 percent to 70 percent of all HCC tumors showed an abnormal accumulation of this "oncoprotein" within the cell, Hung says.

What Hung and his team of researchers investigated was just how HBV results in accumulation and activation of the beta catenin oncoprotein. To do that, Qingqing Ding, M.D., a postdoctoral fellow in Hung’s lab, initiated experiments to investigate the chain of molecular events that links how HBX, a gene encoded by HBV virus, "upregulates" beta catenin.

What they found is that HBX shuts down GSK-3ß, whose role is to degrade the beta catenin proteins that enter the interior of a cell. Therefore, GSK-3ß functions as a tumor suppressor, and when it is inactive, beta catenin accumulates in the cell cytoplasm and nucleus. They also resolved a puzzle regarding the relationship between GSK-3ß and Erk, a well-known enzyme frequently activated in human cancers. Erk interacts with and phosphorylates GSK-3ß at a specific amino acid residue Thr 43, resulting in degradation and thus inactivation of GSK-3ß.

"When GSK-3ß becomes inactive, then beta catenin is over-expressed," Hung says. "This is important because beta catenin over-expression is found in many cancer types."

But Hung says the investigators found "a way to turn this around." In current research, they have created a super-active mutant of the GSK-3ß gene at amino acid residue Thr 43. By adding this gene into liver cancer cells, over-expression of beta catenin was downregulated, therefore, proliferation of cancer cells will be inhibited. Based on this finding, "we think it may be possible in the near future to develop novel therapeutic approaches for treatment of the aforementioned cancers including development of gene therapy and a small molecule that will activate GSK-3ß," he says.

Nancy Jensen | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Studies and Analyses:

nachricht Real-time feedback helps save energy and water
08.02.2017 | Otto-Friedrich-Universität Bamberg

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>