Malignant melanoma in liver tissue
Liver cells shut down to protect themselves from cancer. And in a perfect world, senescence gives the body time to repair damage or eliminate damaged cells before they can become cancerous. However, that’s not what happens in liver cells, a new study finds.
A team of researchers at the University of California has shed new light on the development of liver cancer, the sixth most frequently diagnosed cancer and the fourth cause of death for cancer worldwide.
O, published in the magazine Naturereveals a complex interaction between the cellular metabolism and DNA damage that drive the progression of fatty liver disease to cancer.
The results suggest new avenues for preventing and treating liver cancer and have significant implications for our understanding of the origins of cancer and the effects of diet on our DNA.
The incidence of the most common form of liver cancer, hepatocellular carcinoma (CHC), has increased 25-30% over the past two decades, with much of the growth attributed to the dramatic rise in fatty liver disease, which currently affects 25% of American adults.
Nearly 20% of individuals with liver disease fatty tissue present a severe form of the disease, called steatohepatitis associated with metabolic dysfunction (MASH), which considerably increases the risk of HCC. However, how MASH transitions to liver cancer is not well understood.
“Going from fatty liver disease to MASH to liver cancer is a very common scenario and theThe consequences can be deadly“explains Michael Karinprofessor at the University of California School of Medicine and lead author of the study, in a statement published on .
“When you have MASH, or if it ends up destroying the liver and if you need a new liver, or if it progresses to an often fatal liver cancerbut we still don’t understand what is happening at the subcellular level during this process”, adds Karin.
The researchers used a combination of mouse models and human tissue specimens and databases to demonstrate that MASH-inducing diets, which are high in fat and sugar, give us the reason no ADN of liver cells which causes them to enter senescence, a state in which the cells are still alive and metabolically active but can no longer divide.
Senescence is a normal response to a variety of cellular stress factors. In a perfect world, senescence gives the organism time to repair damage or eliminate damaged cells before they can proliferate more widely and become cancerous.
However, as researchers discovered, that’s not what happens in liver cells, also known as hepatocytes. In hepatocytes, some damaged cells survive this process.
These cells are, according to Karin, “like time bombs that can start to proliferate again at any time and, ultimately, become cancerous.”
“Exhaustive genomic analyzes of tumor DNA indicate that they originate from liver cells damaged by MASH, which underlines a direct link between diet-induced DNA damage and the development of cancer,” he adds. Ludmil Alexandroprofessor of Cellular and Molecular Medicine and Bioengineering at the same university, and co-author of the study.
The findings suggest that developing new drugs to prevent or reverse DNA damage may be a promising therapeutic approach to preventing liver cancer, particularly in people with MASH.
“They exist some possibilities how this can be used for future treatment, but more time and research will be needed to explore these ideas”, said Karin.
“One hypothesis is that a high-fat diet can lead to an imbalance in the raw materials that our cells use to build and repair DNA and that we can use nutritional medicines or chemicals to correct these imbalances”, says Karin
“Another idea is to development of new antioxidantsmuch more efficient and specific than the ones we have now, and their use could help block or reverse cellular stress that causes DNA damage”, he adds.
In addition to opening new avenues of treatment for liver cancer, the study offers new insights into the relationship between aging and cancer.
“We know that aging increases the risk of virtually all cancers and that aging is associated with cellular senescence, but this introduces a paradox, since senescence is supposedly a protectiveagainst cancer”, said Karin.
“This study helps reveal the underlying molecular biology that allows cells to re-enter the cell cycle after undergoing senescence, and we believe that similar mechanisms may be at work in a wide range of cancers.”
The results also help to directly quantify harmful effects of a diet poor in cellular metabolism, which, according to Karin, could be used to help guide public health messages related to fatty liver disease.
“A poor, fast-food diet can be just as dangerous such as long-term cigarette consumption,” said Karin. “People need to understand that bad diets do much more than just change a person’s aesthetic appearance. They can fundamentally alter the functioning of our cells, right down to their DNA.”
