Sugar Metabolism in Liver Implicated in Liver Cancer Diagnosis

Liver tumors found to stop using fructose.

Monitoring sugar metabolism in the liver could be a new and significant diagnostic marker for liver cancer, a recent study found.

The study, published in Nature Cell Biology, indicates that the gene ketohexokinase or fructokinase (KHK) expresses differently in normal liver tissues compared with liver tumors.

Liver cancer cells were found to have a significantly reduced level of fructose metabolism compared with healthy cells.

“Normal liver cells catalyze both glucose and fructose for energy, amino acid and lipid production,” said researcher Zhimin Lu, MD, PhD. “However, we found that liver tumors stopped using fructose. Thus, monitoring fructose metabolism could potentially be used for liver cancer diagnosis.”

This reduction of fructose metabolism in liver tumors cells is caused by aberrant alternative splicing of the KHK gene. This process results in the expression in a variety of the gene product KHK-A, which lost the ability to process fructose.

“KHK-A has 2 enzymatic activities, sugar kinase and protein kinase,” Lu said. “We discovered that KHK-A was not only a sugar kinase but also a protein kinase.”

The study was able to show that KHK-A’s protein kinase activity enhances tumor cell DNA and RNA synthesis.

“It is this protein kinase activity that we believe can be targeted to treat the liver tumor,” Lu said. “Our study revealed a pivotal mechanism underlying how liver and liver tumor cells use fructose and highlight the instrumental role of the KHK-A protein in promoting tumor development.”