Monitoring sugar metabolism in liver may be a key to cancer diagnosis

Study shows that normal and cancerous liver cells metabolize dietary fructose differently

MD Anderson News Release April 18, 2016

Scientists may have discovered a significant new diagnostic marker for liver cancer, according to a paper published in the April 18 online issue of .

A study led by Â鶹ӳ»­ MD Anderson Cancer Center 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 , professor of Neuro-Oncology. ¡°However, we found that liver tumors stopped using fructose. Thus, monitoring fructose metabolism could potentially be used for liver cancer diagnosis.¡±

Lu¡¯s 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.

¡°KHK-A has two enzymatic activities, sugar kinase and protein kinase,¡± said Lu. ¡°We discovered that KHK-A was not only a sugar kinase but also a protein kinase.¡±

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,¡± he 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.¡±

MD Anderson study team participants included Xinjian Li, Ph.D., Xu Qian, Ph.D., Yuhui Jiang, Ph.D., Yanhua Zheng, Ph.D., Yan Xia, Ph.D. and Jong-Ho Lee, Ph.D., all of Neuro-Oncology; David Hawke, Ph.D., Systems Biology; and Gilbert Cote, Ph.D., Endocrine Neoplasia and Hormonal Disorders.

Other participating institutions included Sun Yat-Sen University Cancer Center, Guangzhou, China; Shanghai Jiaotong University, Shanghai; and Â鶹ӳ»­ Graduate School of Biomedical Sciences, Houston.