Oncotarget

Research Papers:

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

Kyoungsub Song, Hyunjoo Kwon, Chang Han, Jinqiang Zhang, Srikanta Dash, Kyu Lim and Tong Wu _

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Oncotarget. 2015; 6:40822-40835. https://doi.org/10.18632/oncotarget.5812

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Abstract

Kyoungsub Song1, Hyunjoo Kwon1, Chang Han1, Jinqiang Zhang1, Srikanta Dash1, Kyu Lim2, Tong Wu1

1Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA

2Department of Biochemistry, College of Medicine, Cancer Research Institute and Infection Signaling Network Research Center, Chungnam National University, Daejeon, Korea

Correspondence to:

Tong Wu, e-mail: twu@tulane.edu

Keywords: CD133, cancer stem cells, glycolysis, miR-122

Received: March 13, 2015     Accepted: September 23, 2015     Published: October 19, 2015

ABSTRACT

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.


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