CMU President Mien-Chie Hung and His International Research Team Discovered a New Target Therapy for Liver Cancer Treatment that Published in the Prestigious Journal "Nature"
Date：April 9, 2020
Good news for liver cancer patients! China Medical University (CMU) President Mien-Chie Hung led an international research team that made a breakthrough discovery: the gluconeogenic metabolic enzyme PCK1 has protein kinase activity and can be used as a new target for liver cancer treatment. This research “The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis” was published in the journal Nature (impact factor 43.07) and has pointed out a new direction for precision treatment for liver cancer.
PCK1 (phosphoenolpyruvate carboxykinase 1) is a key metabolic enzyme for Gluconeogenesis in liver and kidney. Its main function is to convert OAA (oxaloacetate) into PEP (phosphoenolpyruvate). This process of converting non-carbohydrates into glucose is an important physiological mechanism for maintaining the balance of blood sugar. Previous studies has also pointed out that PCK1 is an important tumor suppressor gene, showing that PCK1 plays a crucial role in physiological balance and cancer prevention.
However, the team found that under abnormal growth stimulation, cancerous liver cell will cause the phosphorylation of PCK1 through the AKT signaling pathway. This changes the function of PCK1 and led to the mechanism of lipogenesis, resulting in the massive production of cholesterol and fatty acid that directly facilitate cancer development. “The best significance of this research is to discover that PCK1, which should have been a tumor suppressor gene, was transformed into a carcinogen during the canceration process. This is completely different from its original function. Besides, when this kind of PCK1 phosphorylates the downstream molecule Insig1/2, GTP is used as the phosphate source rather than the common ATP, this is also very special,” said President Hung.
In clinical application, the phosphorylated PCK1 formed by cancer cells will be the most ideal therapeutic target, due to the drugs that inhibit phosphorylated PCK1 will only kill cancer cells without affecting normal cells. This is an important breakthrough point for future research since there is no available drugs currently. Moreover, the team pointed out that in addition to liver cancer cells, the same PCK1 phosphorylation was found in other cancer cells, which means that this new strategy is expected to be widely used in various cancer groups and has great clinical value.
This research pointed out a new direction for new drug development and showed that the canceration turning point of phosphorylated PCK1 itself is the best drug target. With this new finding, it is expected that the treatment for liver cancer will be strengthened and bring a breakthrough in the history of precision medicine research.