Active glycolytic metabolism in CD133(+) hepatocellular cancer stem cells: regulation by MIR-122

作者：Song Kyoungsub; Kwon Hyunjoo; Han Chang; Zhang Jinqiang; Dash Srikanta; Lim Kyu; Wu Tong^*

来源：Oncotarget, 2015, 6(38): 40822-40835.

DOI：10.18632/oncotarget.5812

• CD133
• cancer stem cells
• glycolysis
• miR-122

Although altered metabolic pathway is an important diagnostic maker and therapeutic target in cancer, it is poorly understood in cancer stem cells (CSCs). Here we show that the CD133 (+) hepatocellular CSCs have distinct metabolic properties, characterized by more active glycolysis over oxidative phosphorylation, compared to the CD133 (-) cells. Inhibition of PDK4 and LDHA markedly suppresses CD133 (+) stemness characteristics and overcome resistance to sorafenib (current chemotherapeutic agent for hepatocellular cancer). Addition of glucose or lactate to CD133 (-) cells promotes CSC phenotypes, as evidenced by increased CD133 (+) cell population, elevated stemness gene expression and enhanced spheroid formation. Furthermore, the liver-specific miRNA, miR-122, inhibits CSC phenotypes by regulating glycolysis through targeting PDK4. Our findings suggest that enhanced glycolysis is associated with CD133 (+) stem-like characteristics and that metabolic reprogramming through miR-122 or PDK4 may represent a novel therapeutic approach for the treatment of hepatocellular cancer.

• 出版日期2015-12-1