COVID-19 updates, including vaccine information, for our patients and visitors Learn More

Menu
Search

Scientists Uncover Protective Mechanism Against Liver Cancer

 

December 14, 2009  |  

A team of scientists from the UC San Diego School of Medicine and Osaka University in Japan have identified a protein switch that helps prevent liver damage, including inflammation, fibrosis and cancer. The findings suggest that a better understanding of how the protein, TAK1, works could lead to new insights into the development of liver disease and cancer.

“TAK1 appears to be a master regulator of liver function,” said David A. Brenner, MD, professor of medicine and Dean of the UC San Diego School of Medicine. He and Ekihiro Seki, MD, PhD, assistant research scientist in the Department of Medicine, led the work. “Understanding its role in liver disease and cancer may eventually enable us to devise new therapeutic strategies.” Their study appears on line the week of December 14 in advance of publication in the journal Proceedings of the National Academy of Sciences.

TAK1 is a kinase, a type of signaling protein involved in regulating various cell activities, including cell growth. Researchers have known that TAK1 activates two specific proteins, NF-kappaB and JNK, which are both involved in immunity, inflammation, programmed cell death and cancer. But NF-kappaB helps protect liver cells from dying and protects against cancer development. In contrast, JNK promotes cell death and cancer.

However, it has been unclear whether TAK1 promotes or prevents the development of liver cancer. To find out, Seki, Brenner and their group created a mouse model in which liver cells lacked the gene Tak1, which makes the TAK1 protein. In a series of experiments, they found a high rate of liver cell death in young animals lacking TAK1. The animals’ livers then went into overdrive, producing too many liver cells to make up for the loss and causing liver damage, including inflammation and fibrosis – liver scarring – and eventually, cancer.

According to Seki, the study is the first to demonstrate the role of TAK1 in cancer development, and strongly suggests that the protein also contributes to cancer development in other organs. In addition, the liver cancer mouse model that the team developed is associated with sustained liver inflammation and fibrosis – key features of human liver cancer – and should be useful in investigating whether fibrosis influences liver cancer development.

“We can also use the model to test whether a potential cancer drug or therapy affects both fibrosis and cancer, or either one,” Seki said. “This study will open a new therapeutic potential targeting the expression of TAK1 for liver cancer.”

Additional contributors include Sayaka Inokuchi, Tomonori Aoyama, Kouichi Miura, Christoph H. Osterreicher, Yuzo Kodama, UCSD Department of Medicine; Katsumi Miyai, UCSD Department of Pathology; and Shizuo Akira, Osaka University.

This study was funded by grants from the American Association for the Study of Liver Diseases/American Liver Foundation, the National Institute on Alcohol Abuse and Alcoholism and the National Institutes of Health.

# # #

Media Contact: Steve Benowitz, 619-543-6163, sbenowitz@ucsd.edu

 

 

 

 

 




Media Contact

Share This Article


Related News

8/2/2021
UC San Diego researchers modify remdesivir, creating oral version that can be taken earlier in COVID-19 diagnoses. In cell and animal studies, revised drug proved effective and safe.
7/28/2021
Obesity is a major public health issue among Latinos, and a risk factor for Alzheimer’s disease. But in a new study, researchers at UC San Diego report that cardiometabolic abnormalities, such as hype ...
7/28/2021
Cardiovascular physicians with UC San Diego Health have joined an international clinical trial utilizing a new Extravascular Implantable Cardioverter-Defibrillator (EV ICD) system to help treat sudden ...
7/26/2021
UC San Diego Health, the region’s only academic health system, is ranked #1 in San Diego and #5 in California, placing it among the nation’s best hospitals, according to the 2021-2022 U.S. News & Worl ...



Follow Us