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2-Deoxy-d-Glucose-Induced Metabolic Alteration in Human Oral Squamous SCC15 Cells: Involvement of N-Glycosylation of Axl and Met

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Author(s)
Naeun LeeWon-Jun JangJi Hae SeoSooyeun LeeChul-Ho Jeong
Keimyung Author(s)
Seo, Ji Hye
Department
Dept. of Biochemistry (생화학)
Journal Title
Metabolites
Issued Date
2019
Volume
9
Issue
9
Keyword
glycolysisN-linked glycosylation2-deoxy-d-glucoseoral cancercancer metabolism
Abstract
One of the most prominent hallmarks of cancer cells is their dependency on the glycolytic pathway for energy production. As a potent inhibitor of glycolysis, 2-deoxy-d-glucose (2DG) has been proposed for cancer treatment and extensively investigated in clinical studies. Moreover, 2DG has been reported to interfere with other biological processes including glycosylation. To further understand the overall effect of and metabolic alteration by 2DG, we performed biochemical and metabolomics analyses on oral squamous cell carcinoma cell lines. In this study, we found that 2DG more effectively reduced glucose consumption and lactate level in SCC15 cells than in SCC4 cells, which are less dependent on glycolysis. Coincidentally, 2DG impaired N-linked glycosylation of the key oncogenic receptors Axl and Met in SCC15 cells, thereby reducing the cell viability and colony formation ability. The impaired processes of glycolysis and N-linked glycosylation were restored by exogenous addition of pyruvate and mannose, respectively. Additionally, our targeted metabolomics analysis revealed significant alterations in the metabolites, including amino acids, biogenic amines, glycerophospholipids, and sphingolipids, caused by the impairment of glycolysis and N-linked glycosylation. These observations suggest that alterations of these metabolites may be responsible for the phenotypic and metabolic changes in SCC15 cells induced by 2DG. Moreover, our data suggest that N-linked glycosylation of Axl and Met may contribute to the maintenance of cancer properties in SCC15 cells. Further studies are needed to elucidate the roles of these altered metabolites to provide novel therapeutic targets for treating human oral cancer.
Keimyung Author(s)(Kor)
서지혜
Publisher
School of Medicine (의과대학)
Citation
Naeun Lee et al. (2019). 2-Deoxy-d-Glucose-Induced Metabolic Alteration in Human Oral Squamous SCC15 Cells: Involvement of N-Glycosylation of Axl and Met. Metabolites, 9(9). doi: 10.3390/metabo9090188
Type
Article
ISSN
2218-1989
Source
https://www.mdpi.com/2218-1989/9/9/188
DOI
10.3390/metabo9090188
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/42391
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
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