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 show...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/287381 |
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| author | Hong-tao Song Yu Qin Guo-dong Yao Zhen-nan Tian Song-bin Fu Jing-shu Geng |
| author_facet | Hong-tao Song Yu Qin Guo-dong Yao Zhen-nan Tian Song-bin Fu Jing-shu Geng |
| author_sort | Hong-tao Song |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1faae2bc7be1444dbee2c894f7602da7 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-1faae2bc7be1444dbee2c894f7602da72025-08-20T03:54:34ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/287381287381Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK SignalingHong-tao Song0Yu Qin1Guo-dong Yao2Zhen-nan Tian3Song-bin Fu4Jing-shu Geng5Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, ChinaDepartment of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, ChinaDepartment of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, ChinaDepartment of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, ChinaDepartment of Medical Genetics, Harbin Medical University, Harbin 150086, ChinaDepartment of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin 150040, ChinaTo 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.http://dx.doi.org/10.1155/2014/287381 |
| spellingShingle | Hong-tao Song Yu Qin Guo-dong Yao Zhen-nan Tian Song-bin Fu Jing-shu Geng Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling Mediators of Inflammation |
| title | Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling |
| title_full | Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling |
| title_fullStr | Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling |
| title_full_unstemmed | Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling |
| title_short | Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling |
| title_sort | astrocyte elevated gene 1 mediates glycolysis and tumorigenesis in colorectal carcinoma cells via ampk signaling |
| url | http://dx.doi.org/10.1155/2014/287381 |
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