Malignant liver cell carcinoma: fat production promotes tumor formation
According to health experts, liver cancer is the second leading cause of cancer-related death worldwide and the fastest growing cancer. Researchers have now found that tumor formation is promoted by fat production. Her investigation shows that drugs that specifically target the formation of fats have the potential to interrupt tumor development.
Liver cancer from chronic liver diseases
Liver cancer is the second leading cause of cancer-related death worldwide and the fastest growing cancer. According to health experts, the tumor develops in most cases in patients with chronic liver diseases. It is known that the risk of liver cancer and liver cirrhosis increases, among other things, through a so-called fatty liver, which is due, for example, to diet-related or genetically caused fat metabolism disorders or excessive alcohol consumption. In addition, scientific studies have shown that obesity and type 2 diabetes increase the risk of liver cancer. Researchers from Switzerland have now found that tumor formation is promoted by fat production.
Cancer cells need fat compounds
Fat compounds, also called lipids, are optimal sources of energy and provide important building materials for the cell. Fast and uncontrolled growing cancer cells need a lot of it.
Researchers from the Biozentrum of the University of Basel and the University of Geneva have now found that the protein mTOR stimulates the production of lipids in liver tumors, among other things to satisfy the increased nutrient turnover and energy requirements of cancer cells.
This process was also observed in patients with liver cancer, as the researchers report in the specialist magazine "Cancer Cell".
The occurrence of liver cell carcinoma has doubled
According to a statement from the University of Basel, the incidence of malignant and aggressive liver cell carcinoma, especially in industrialized countries, has doubled over the past twenty years.
One of the possible reasons for this is the increase in obesity and diabetes.
Scientists led by Prof. Michael N. Hall from the Biozentrum of the University of Basel and Prof. Howard Riezman from the University of Geneva have now gained new knowledge about the development of this tumor.
Using the mouse model and patient samples, they were able to demonstrate that the growth regulator mTOR - mammalian target of rapamycin - stimulates the resynthesis of lipids, which leads to disease progression.
The accumulation of fatty acids and fats in the liver is one of the most common causes of liver cell carcinoma.
The course of the disease was first examined in the mouse model
The researchers first examined the course of the disease in a mouse model. To do this, they permanently activated mTOR in the liver cells.
“We already knew that mTOR is involved in the development of tumors as a control body for cell growth. In the case of liver cell carcinoma, however, we didn't know which cellular metabolic pathways were affected, ”explains Guri.
The scientists have now found that mTORC2 - mTOR can occur in two protein complexes, mTORC1 and mTORC2 - triggers the new synthesis of fatty acids and certain lipids.
“Most people are not even aware that there are more lipids than genes in our bodies. Thousands of different types of lipids are assumed, ”says Guri. "Together with the Howard Riezman team, we were able to analyze a very broad spectrum of lipids."
Stop tumor development
In the liver cells, mTORC2 particularly stimulates the formation of two types of lipids that are important for cell growth: the sphingolipids and cardiolipins.
The former are, among other things, important components of the cell membrane, which have to be replenished continuously in the event of uncontrolled tumor cell growth.
The cardiolipins are located in the cell's power plants, the mitochondria, and are involved in energy generation. With an increased cardiolipin production, the energy-eating tumor cells ensure the energy supply.
"Cancer cells rely on the new synthesis of fatty acids and lipids, if you turn the tap off you can stop the development of tumors."
Patients: analysis of liver biopsies confirmed association
Examinations of tissue samples taken from patients with hepatocellular carcinoma confirmed the observations made in the mouse model.
Also in tissue samples from the human liver, mTORC2 and the subsequent signaling pathways, which force a new production of fatty acids and lipids, are activated.
In this way, the protein complex drives the progression of the disease from the benign changed "fatty liver" to the aggressive liver cell tumor (HCC).
The study provides important insights because it shows that drugs that specifically target the formation of fats have the potential to interrupt tumor development. (ad)