Liver Cancer May Be Diagnosed from Altered Sugar Metabolism

This resulted in expression of a variety of the gene product called KHK-A, which lost the ability to process fructose. The team showed that KHK-A’s protein kinase activity enhanced tumor cell DNA and ribonucleic acid (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.

The team found that, KHK-A acts as a protein kinase, phosphorylating and activating phosphoribosyl pyrophosphate synthetase 1 (PRPS1) to promote pentose phosphate pathway-dependent de novo nucleic acid synthesis and HCC formation. Furthermore, the V-Myc Avian Myelocytomatosis Viral Oncogene Homolog (c-Myc), Heterogeneous Nuclear Ribonucleoprotein H1/2 (hnRNPH1/2) and KHK-A expression levels and PRPS1 Thr225 phosphorylation levels correlate with each other in HCC specimens and are associated with poor prognosis for HCC.

The authors concluded that their findings reveal a pivotal mechanism underlying the distinct fructose metabolism between HCC cells and normal hepatocytes and highlight the instrumental role of KHK-A protein kinase activity in promoting de novo nucleic acid synthesis and HCC development. Zhimin Lu, MD, PhD, a professor of neuro-oncology and senior author of the study said, “It is this protein kinase activity that we believe can be targeted to treat the liver tumor. 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.” The study was published on April 18, 2016, in the journal Nature Cell Biology.

Related Links:
University of Texas MD Anderson Cancer Center