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-3â, which acts to suppress tumor formation as well as inhibit the spread of cancer.
GSK-3â 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.