Summary of Hidden Hero Identified – Researchers Flip the Script on Liver Cancer:
Scientists at UC San Diego have discovered that the protein ATF4, previously associated with advanced liver cancer, protects the liver against hepatocyte death and subsequent tumor formation. This unexpected finding could inspire new clinical strategies for preventing liver disease and cancer. The study suggests that ferroptosis, an iron-dependent form of liver cell death, maybe the most relevant form of hepatocyte death that leads to inflammation, compensatory proliferation, and cancer in the liver. The researchers believe that ferroptosis inhibitors or ATF4 activators may be clinically helpful in preventing steatohepatitis and its progression to cancer.
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UC San Diego Scientists Discover Protein that May Prevent Liver Cancer
Liver cancer is a deadly cancer affecting millions worldwide, making it a significant public health issue. According to the World Health Organization (WHO), liver cancer is the sixth most common type of cancer globally and the third leading cause of cancer deaths globally. Fortunately, recent research conducted by scientists at UC San Diego has identified a protein that may prevent liver cancer.
Environmental factors and metabolic stressors, such as obesity, virus hepatitis, and steatohepatitis, can cause liver cell death and damage, leading to inflammation and eventual cancer. Activating transcription factor 4 (ATF4), a key mediator of the liver stress response is a protein previously linked to advanced liver cancer. However, this new study shows that ATF4 protects the liver against hepatocyte death and tumor formation.
The unexpected results of this study suggest that ATF4 may play an essential role in preventing liver disease and cancer. The study authors believe their findings could inspire new clinical strategies for preventing liver cancer.
The study was recently published in the Journal of Hepatology. It was led by senior authors Michael Karin, Ph.D., Distinguished Professor of Pharmacology and Pathology at UC San Diego School of Medicine, and Benjamin C. Yaden, Ph.D., associate vice president of Diabetes Novel Therapies and External Innovation at Eli Lilly.
How ATF4 protects the 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 exposed to various stressors to promote liver damage and tumor formation.
The results showed that ATF4-deficient mice showed more hepatocyte cell death, inflammation, compensatory cellular proliferation, and accelerated liver cancer development. This suggested that ATF4 protected against liver cancer in some way.
Further experiments confirmed that ATF4 promoted the expression of SLC7A11, a protein that helps maintain hepatocyte homeostasis. SLC7A11 helps suppress a specific type of cell death called ferroptosis. By reducing the amount of ferroptosis, the ATF4-SLC7A11 axis protects hepatocytes and slows the progression from liver damage to liver cancer.
The researchers found that ferroptosis may be the most relevant form of hepatocyte death that leads to inflammation, compensatory proliferation, and cancer in the liver. This suggests that ferroptosis inhibitors or ATF4 activators may be clinically helpful in preventing steatohepatitis and its progression to cancer.
Implications of the study
The study sheds light on the crucial role of ATF4 in liver disease and cancer development. The findings challenge the previously held notion that ATF4 promotes liver cancer. Instead, the research suggests that ATF4 may be a critical factor in inhibiting liver cancer.
The study results offer insights into the mechanism behind liver damage and cancer progression. Clinical applications of these findings may lead to new treatments or therapies that target the ATF4-SLC7A11 axis to inhibit ferroptosis and prevent liver cancer.
Conclusion
The discovery of ATF4’s role in preventing liver disease and cancer development offers new insights into the mechanisms behind liver damage and cancer progression. By understanding how this protein works, clinicians may be able to develop new treatments and therapies to prevent and control liver disease and cancer. Further research is needed to fully understand the potential of this discovery and its implications for public health.
