Astrocyte elevated gene-1 mediates glycolysis and tumorigenesis in colorectal carcinoma cells via AMPK signaling.
To investigate the role of AEG-1 in glycolysis and tumorigenesis, we construct myc-AEG-1 expression vector and demonstrate a novel mechanism that AEG-1 may increase the activity of AMPK by Thr172 phosphorylation. The higher expression levels of AEG-1 in colorectal carcinoma cells were found but showed significant difference in different cell lines. To study the role of AEG-1 in colorectal cells, myc-AEG-1 vector was constructed and transfected into NCM460 colonic epithelial cells. We observed consistent increasing of glucose consumption and lactate production, typical features of anaerobic glycolysis, suggesting that AEG-1 may promote anaerobic glycolysis. Moreover, we noted that AMPK phosphorylation at Thr172 as well as pPFK2 (Ser466) was increased in NCM460 cells overexpressing AEG-1. Compound C may block AMPK and PFK2 phosphorylation in both control and AEG-1-overexpressed cells and decrease the glucose consumption and lactate production. The present findings indicated that reduced AEG-1 protein levels by RNAi may decrease the glucose consumption and lactate production in HCT116 colorectal carcinoma cells. The present identified AEG-1/AMPK/PFK2 glycolysis cascade may be essential to cell proliferation and tumor growth. The present results may provide us with a mechanistic insight into novel targets controlled by AEG-1, and the components in the AEG-1/AMPK/PFK2 glycolysis process may be targeted for the clinical treatment of cancer.
Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, China.
Hong-tao
HT
Song
Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, China.
Yu
Y
Qin
Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, China.
Guo-dong
GD
Yao
Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, China.
Zhen-nan
ZN
Tian
Department of Medical Genetics, Harbin Medical University, Harbin 150086, China.
Song-bin
SB
Fu
Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, China ; Department of Medical Genetics, Harbin Medical University, Harbin 150086, China.
Jing-shu
JS
Geng
D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D055372:AMP-Activated Protein Kinases