A study published in the journal Nature Cell Biology found that a gene known as KHK (ketohexokinase or fructokinase) is expressed differently in normal liver tissues versus liver tumors. The findings reveal that liver cancer cells had a much reduced level of fructose metabolism versus healthy cells.
"Normal liver cells catalyze both glucose and fructose for energy, amino acid and lipid production," said tha author. "However, we found that liver tumors stopped using fructose. Thus, monitoring fructose metabolism could potentially be used for liver cancer diagnosis."
The team discovered that reduced fructose metabolism in liver tumor cells is caused by aberrant alternative splicing of the KHK gene. This resulted in expression of a variety of the gene product called KHK-A, which lost the ability to process fructose.
"We discovered that KHK-A was not only a sugar kinase but also a protein kinase," said the author.
The team showed that KHK-A's protein kinase activity enhanced tumor cell DNA and RNA synthesis and newly identified KHK-A as essential for liver tumor formation. Kinases are enzymes that allow cells to transfer phosphate, crucial for energy production and protein regulation.
"It is this protein kinase activity that we believe can be targeted to treat the liver tumor," author 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."
A new diagnostic marker for liver cancer?
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