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Published on: July 21, 2018
Insulin promotes hepatocarcinoma tumorigenesis by up-regulating PKM2 expression
Jingjing Liu1, Qiang Zhi2, Yunpeng Liu1
1Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, 201 Hubin South Road, Xiamen, 361004, Fujian Province, PR China; Xiamen Key Laboratory of Intestinal Microbiome and Human Health, Zhongshan Hospital Affiliated to Xiamen University, 201 Hubin South Road, Xiamen, 361004, Fujian Province, PR China.
Abstract:
Insulin, as a growth factor, can increase the risk of certain types of cancer. The present study showed that insulin promoted the proliferation of hepatocellular carcinoma cells in vitro and in vivo through pyruvate kinase M2 (PKM2), which is a rate-limiting enzyme in the process of glycolysis. Moreover, the expression of PKM2 was up-regulated by insulin at the posttranslational level in a nuclear orphan receptor TR3-dependent manner. In addition, insulin could enhance the interaction between PKM2 and TR3 and protect PKM2 from degradation. Our results identified a specific mechanism of insulin affecting cancer metabolism and thus promoting cancer progression, and they contribute to a better understanding of the observation that insulin is linked to an increased cancer risk under hyperinsulinemic conditions.
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