Liver cancer tumor development is favored by fat

Malignant hepatocellular carcinoma: Fat production promotes tumor formation

According to health experts, liver cancer is the second most common cause of cancer death worldwide and the fastest growing incidence of cancer. Researchers have now found that tumor formation is promoted by fat production. Their study shows that drugs that target the formation of fats have the potential to disrupt tumor development.

Liver cancer due to chronic liver disease

Liver cancer is the second most common cause of cancer death worldwide and the highest rate of cancer. According to health experts, the tumor usually develops in patients with chronic liver disease. It is known that the risk of liver cancer and liver cirrhosis is increased, inter alia, by a so-called fatty liver, which is due, for example, to dietary or genetically caused disorders of the lipid metabolism or excessive alcohol consumption. In addition, scientific research has suggested that obesity and type 2 diabetes increase the risk of liver cancer. Researchers from Switzerland have now discovered that tumor formation is promoted by fat production.

The occurrence of malignant and aggressive hepatocellular carcinoma has increased enormously, especially in industrialized countries. One of the possible reasons for this is the increase in obesity and diabetes. Researchers have now discovered that tumor formation is promoted by fat production. (Image: blueringmedia / fotolia.com)

Cancer cells need fatty 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, University of Basel and the University of Geneva have now discovered that the protein mTOR stimulates the production of lipids in liver tumors, among other things, to quench the increased nutrient and energy requirements of cancer cells.

This process was also observed in patients with liver cancer, as the researchers report in the journal "Cancer Cell".

Occurrence of hepatocellular carcinoma has doubled

According to a statement from the University of Basel, the incidence of malignant and aggressive hepatocellular carcinoma has doubled in the last 20 years, especially in industrialized countries.

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 insights into the development of this tumor.

In the mouse model and from patient samples, they were able to show that the growth regulator mTOR - mammalian Target of Rapamycin - stimulates the lipid synthesis, which leads to a progression of the disease.

The accumulation of fatty acids and fats in the liver is one of the most common causes of hepatocellular carcinoma.

Disease course first examined in the mouse model

The researchers first examined the course of the disease in a mouse model. For this they have permanently activated mTOR in the liver cells.

"We already knew that mTOR is involved in the development of tumors as a cell growth control agent. However, in the case of hepatocellular carcinoma, we did not know which cellular metabolic pathways were affected, "explains Guri.

The scientists have now discovered that mTORC2 - mTOR can be found in two protein complexes, mTORC1 and mTORC2 - initiating the re-synthesis of fatty acids and certain lipids.

"Most people are unaware that there are more lipids in our body than genes. Thousands of different types of lipids are used, "says Guri. "Together with Howard Riezman's team, we were able to analyze a very wide range of lipids."

Stop development of tumors

In liver cells, mTORC2 in particular stimulates the formation of two important lipid types for cell growth: sphingolipids and cardiolipins.

The former are, among other things, important components of cell membranes, which constantly have to be replenished 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 production. With increased cardiolipin production, the energy-eating tumor cells ensure energy supply.

"Cancer cells rely on the re-synthesis of fatty acids and lipids, turning them on can stop the development of tumors."

Patients: analysis of liver biopsies confirmed association

Examination of tissue samples taken from patients with hepatocellular carcinoma confirmed the observations made in the mouse model.

Tissue samples from the human liver also activate mTORC2 and subsequent signaling pathways that promote new production of fatty acids and lipids.

In this way, the protein complex is driving the progression of the disease from benign altered "fatty liver" to 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 disrupt tumor development. (Ad)