Protein (ATF4) Associated with Liver Cancer May Actually Be Key to Protecting Against It

Liver cancer is the third leading cause of cancer death and the sixth most common cancer type worldwide. Major risk factors include environmental and metabolic stressors, such as obesity, viral hepatitis, and steatohepatitis (fatty and inflamed liver). These stressors damage the liver by killing hepatocytes, the major cell type in the liver. The cell death then triggers an inflammatory response that signals the liver to generate a new batch of hepatocytes. But this sudden push towards cellular proliferation also increases the risk of tumor formation. In a new study, scientists at University of California San Diego School of Medicine investigated the role of activating transcription factor 4 (ATF4), a key mediator of the liver stress response. Despite being previously associated with advanced liver cancer, the researchers found that ATF4 actually protected the liver against hepatocyte death and subsequent tumor formation. The unexpected results could now inspire new clinical strategies for preventing liver disease and cancer. The study, published as an open-access article on March 28, 2023 in the Journal of Hepatology, was led by senior authors Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at UC San Diego School of Medicine and Benjamin C. Yaden, PhD, Associate Vice President of Diabetes Novel Therapies and External Innovation at Eli Lilly.