UC San Diego scientists find the protein ATF4 prevents liver damage and its progression to cancer by blocking ferroptosis, an iron-dependent form of liver cell death. Credit: UC San Diego Health Sciences
Liver cancer is the sixth most prevalent form of cancer and the third leading contributor to cancer fatalities across the globe. It primarily arises from an interplay of environmental factors and metabolic stressors, like obesity, viral hepatitis, and steatohepatitis, which is characterized by a fatty and inflamed liver.
ATF4 levels are typically low in healthy cells, but are elevated when the cell experiences stress. To study its role in the progression of liver cancer, researchers developed a mouse model with ATF4-deficient hepatocytes. The mice were then exposed to various stressors to promote liver damage and tumor formation.
Further experiments led by postdoctoral fellow Feng He, Ph.D., confirmed that ATF4 promoted the expression of SLC7A11, a protein that helps maintain hepatocyte homeostasis. SLC7A11 then helped suppress a specific type of cell death, called ferroptosis. By reducing the amount of ferroptosis, the ATF4-SLC7A11 axis protected hepatocytes and slowed the progression from liver damage to liver cancer.