Scientists at UC San Diego have found that the protein ATF4, previously associated with liver cancer, actually plays a protective role against the disease by preventing ferroptosis, an iron-dependent cell death. Liver cancer, the sixth most common cancer globally, often results from factors such as obesity and viral hepatitis, leading to hepatocyte death, inflammation, and increased tumor growth risks. In their study, researchers created a mouse model lacking ATF4 in hepatocytes and discovered that these mice experienced greater liver cell death, inflammation, and accelerated cancer development when exposed to stressors. This indicated that ATF4 is crucial for liver protection. Further analysis revealed that ATF4 promotes the protein SLC7A11, which maintains hepatocyte health and reduces ferroptosis. The findings suggest that inhibiting ferroptosis or activating ATF4 could offer new clinical strategies for preventing liver disease and cancer progression. The research, published in the Journal of Hepatology, was led by distinguished professors at UC San Diego along with support from various institutions and funding sources. The study emphasizes the relevance of ferroptosis in liver health and its implications for future therapeutic approaches.
