New Role Discovered for Innate Immune Sensor NLPR12: Suppressing Liver Cancer

Researchers at the University of Texas (UT) Southwestern have found that a protein in the body’s innate immune system that responds to gut microbes can suppress the most common type of liver cancer. The study, published online on April 16, 2019 in eLIFE, determined that NLRP12 (Nod-like receptor family pyrin domain containing 12), an innate immune sensor, has a protective effect against hepatocellular carcinoma (HCC), a deadly human cancer associated with chronic inflammation. The open-access article is titled “NLRP12 Suppresses Hepatocellular Carcinoma Via Downregulation of c-Jun N-Terminal Kinase Activation in the Hepatocyte.” HCC is responsible for more than 80 percent of liver cancers in the U.S. It is the third-leading cause of cancer-related deaths worldwide and the ninth-leading cause in America, according to the National Cancer Institute. NLRP12 is a member of the NOD-like family of pattern recognition receptors that help the body sense microbes and other stimuli within the cell to regulate the innate immune response – the body’s first line of defense against infection – in multiple ways. This latest work adds to a growing body of evidence connecting inflammation and the development of tumors in the liver. “In this study, we demonstrated that NLRP12 responds to gut microbes and plays a critical role in suppressing a common form of liver cancer,” said Hasan Zaki (at left in photo), PhD, Assistant Professor of Pathology at UT Southwestern and corresponding author of the study. Major risk factors for HCC include hepatitis B or C viral infection, chronic alcohol abuse, and nonalcoholic fatty liver disease, a condition increasing worldwide along with obesity. Although the precise mechanisms through which these conditions induce liver cancer are unknown, inflammation in the liver is considered a key player.
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