Astrocyte elevated gene-1 mediates glycolysis and tumorigenesis in colorectal carcinoma cells via AMPK signaling.

Hong-Tao Song,Song-Bin Fu,Yu Qin,Guo-Dong Yao,Jing-Shu Geng,Zhen-Nan Tian

doi:10.1155/2014/287381

Abstract

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.

Highlights

The tumorigenesis of cancer cells involves numerous genetic and epigenetic lesions, resulting in the critical alteration of multiple cellular restraints
Results of real-time PCR analysis showed that the transcriptional level of Astrocyte elevated gene-1 (AEG-1) was extremely high in these three colorectal carcinoma cells, increased by 18.7, 20.1, and 22.3-fold in HCT116, HT29, and S/KS cells compared to that of NCM460 (Figure 1(c))
We proposed that ectopic expression of AEG-1 in colon carcinoma cells was responsible for the activated anaerobic glycolysis

Summary

Introduction

The tumorigenesis of cancer cells involves numerous genetic and epigenetic lesions, resulting in the critical alteration of multiple cellular restraints. Most tumor cells exhibit increased glycolysis and take this metabolic pathway as a main source of their energy supply to generate ATP. This is the so-called Warburg effect [4]. Tremendous progress has been made in understanding of the molecular mechanisms of tumorigenesis, especially in the signaling corresponded for its increased glycolysis, such as PI3K-AKTmTOR signaling [5, 6]. It is still largely unknown for the complicated network of increasing glycolysis of tumorigenesis

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Discussion

Conclusion