Liver cancer, one of the world’s leading causes of cancer-related death, may have a surprising ally in the fight against it. Scientists at the University of California at San Diego have identified a Protein ATF4 which can be protective against liver cancer. This pioneering discovery opens up new possibilities for preventing liver disease and cancer.
ATF4:Interaction of factors in the development of liver cancer
Liver cancer is the sixth most common type of cancer worldwide and is strongly influenced by environmental factors and metabolic stressors such as obesity, viral hepatitis, and steatohepatitis. These stressors cause liver cells to die, triggering an inflammatory response and liver regeneration. Unfortunately, this regeneration process also increases the risk of tumor growth.
Exploration du rôle d’ATF4 :
In a recent study published in the Journal of Hepatology, researchers at the University of California, San Diego School of Medicine investigated the activating function of transcription factor 4 (ATF4), a key player in the liver’s response to stress. Contrary to previous beliefs, ATF4 protects the liver from hepatocyte death and tumor formation. This unexpected discovery has the potential to revolutionize clinical approaches to liver disease and cancer prevention.
Understanding the mechanism:
To understand how ATF4 affects the development of liver cancer, the researchers created a mouse model containing ATF4-deficient hepatocytes. They exposed the mice to various stressors to induce liver damage and tumor growth. Surprisingly, ATF4-deficient mice showed increased hepatocyte death, inflammation, compensatory cell proliferation, and rapid development of hepatocellular carcinoma. These results strongly indicate that ATF4 plays a protective role against HCC.
Role of SLC7A11 and Ferroptosis:
Further research by postdoctoral fellow Feng He, Ph.D., has shown that ATF4 enhances the expression of SLC7A11, a protein important for hepatocyte homeostasis. SLC7A11, in turn, helps suppress a specific type of cell death called ferroptosis. By reducing viral hepatitis infection, the ATF4-SLC7A11 pathway protects hepatocytes and slows the progression of HCC from liver lesions. These new insights suggest that targeting viral hepatitis or activating ATF4 could be potential strategies for preventing steatohepatitis and its transformation into carcinoma.
Implications and future possibilities:
The study highlights the importance of viral disease as an important form of liver cell death leading to inflammation, compensatory proliferation and liver cancer. This discovery opens the door to the exploration of iron toxicity inhibitors and ATF4 activators as potential therapeutic interventions. By capitalizing on these discoveries, researchers aim to develop innovative approaches to prevent liver cancer progression and improve patient outcomes.
Funding and collaborators:
The study received funding from the National Institutes of Health Superfund Basic Research Program, the C3 Pedal the Cause grant, the National Natural Science Foundation of China, and the Eli Lilly LIFA program.
The identification of ATF4’s protective role against HCC represents an important advance in this field. This discovery Discovery offers new ways to prevent liver disease and cancer. Scientists can develop more effective strategies to combat HCC by studying ATF4-SLC7A11.