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University of Basel

Liver cancer: How liver cells go astray

overturned wine glass with red wine stain in the shape of a liver
One of the main causes of liver cancer is excessive alcohol consumption. (Photo: Biozentrum, University of Basel)

Liver cancer is one of the most deadly types of cancer. A team of University of Basel researchers has now uncovered how a healthy liver cell turns into a tumor cell. Comprehensive metabolic changes convert mature liver cells into immature progenitor cells. These cells proliferate rapidly and tumors develop.

21 November 2022 | Katrin B├╝hler

overturned wine glass with red wine stain in the shape of a liver
One of the main causes of liver cancer is excessive alcohol consumption. (Photo: Biozentrum, University of Basel)

The causes of liver cancer are manifold. In addition to metabolic disorders such as those associated with obesity, the main causes in the western world are infections with hepatitis C virus and high alcohol consumption. Although liver cell cancer is relatively rare compared to other types of cancer, it is one of the leading causes of cancer-related death, due to poor prognosis.

Like all tumor cells, liver cancer cells proliferate rapidly and in an uncontrolled manner. This requires fundamental changes in their metabolism. In the scientific journal "Molecular Cell", researchers led by Professor Michael N. Hall from the Biozentrum, University of Basel, now report that liver cancer cells reduce the production of a central metabolic molecule. In this way, global metabolism is rewired to enable tumor cells to grow more rapidly.

The liver is the largest metabolic organ in our body. It processes and stores nutrients and detoxifies harmful compounds. When a healthy liver cell turns into a cancer cell, it loses its function. "Tumor cells are selfish. They change their metabolism to grow as quickly as possible," explains cancer researcher Dr. Dirk Mossmann. "At the same time, however, they cease to carry out their tasks as liver cells. That's why liver function is impaired in patients suffering from hepatocellular carcinoma."

Major changes in cell metabolism

The molecule acetyl-CoA plays a central role in cell metabolism. On the one hand, it is the end product of many degradative pathways; on the other, it is needed to produce or chemically modify numerous other molecules. "We found that all acetyl-CoA biosynthesis pathways are downregulated in liver cancer cells," explains first author Dr. Sujin Park. "This results in less acetyl-CoA which in turn affects many other proteins including metabolic enzymes. Such enzymes are functionally altered because they are no longer modified by acetyl-CoA. This can, for example, help tumor cells convert sugar into energy more efficiently."


Original publication

Sujin Park et al.
Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis
Molecular Cell (2022), doi: 10.1016/j.molcel.2022.10.027

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