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A groundbreaking study by researchers at the University of California - San Diego signals potential shifts in understanding liver cancer, unveiling how liver cells' self-defense mechanisms might inadvertently promote cancer development.
This insight is crucial for healthcare professionals in identifying preventive and therapeutic strategies against liver cancer, particularly in patients with high-fat diets and fatty liver disease.
The study by researchers at UC San Diego reveals that liver cells, under stress from high-fat diets, enter a senescent state yet retain the capacity to re-enter the cell cycle, potentially leading to cancer. The research highlights how dietary-induced DNA damage in hepatocytes contributes to hepatocellular carcinoma (HCC) and suggests pathways for new treatments targeting DNA repair mechanisms.
Senescence in liver cells can be misleading as a self-defense mechanism. The study reveals how high-fat diets induce DNA damage in liver cells, pushing them into a state known as cellular senescence. Although senescence typically halts the division of damaged cells to prevent cancer, in liver cells, this defense mechanism appears flawed.
"These cells are, according to Karin, like ticking time bombs that could start proliferating again at any point and ultimately become cancerous."
This observation challenges traditional views of senescence, which is usually seen as a protective measure. In hepatocytes, however, some damaged cells bypass senescence's protective barrier, potentially re-entering the cell cycle and forming cancerous tumors.
High-fat diets significantly contribute to DNA damage in liver cells. The dietary habits prevalent in modern society, especially those rich in fats and sugars, are shown to induce DNA damage in liver cells. This damage perpetuates a cycle where affected cells enter a senescent state but retain the potential for malignancy.
Researchers used both mouse models and human tissue specimens to substantiate these findings. The study illustrates how a MASH-inducing diet can cause irreversible DNA breaks, emphasizing the critical role of nutrition in the genesis of liver cancer.
New therapeutic strategies could focus on reversing the DNA damage instigated by poor diet. The study opens up potential treatment pathways by proposing the development of drugs that could prevent or repair DNA damage. These new drugs or nutri-chemicals might help reverse the DNA damaging effects of high-fat diets and the progression from MASH to cancer.
"One hypothesis is that a high-fat diet could lead to an imbalance in the raw materials our cells use to build and repair DNA, and that we could use drugs or nutri-chemicals to correct these imbalances, said Karin."
The findings also anticipate the development of highly specific antioxidants, which could decrease cellular stress and DNA damage. These strategies, though promising, require extensive research to transition from hypothesis to treatment.
Understanding the links between diet, DNA damage, and cancer should inform public health strategies. The study's insights could significantly contribute to public health initiatives aimed at reducing liver cancer risks. Effective communication about the dangers of high-fat diets and their potential to cause severe DNA damage and cancer could alter public dietary habits.
The researchers emphasize the importance of this information in guiding health messaging. By illustrating parallels between unhealthy dietary habits and smoking, the research hopes to encourage healthier choices, potentially reducing liver cancer prevalence.
Li Gu et al, FBP1 controls liver cancer evolution from senescent MASH hepatocytes, Nature (2025). DOI: 10.1038/s41586-024-08317-9
University of California - San Diego, A 'ticking time bomb' for liver cancer, Medical Xpress (2025). Accessed January 03, 2025. https://medicalxpress.com/news/2025-01-liver-cancer-cells-defense-mechanism.html