Title |
Protein N-glycosylation alteration and glycolysis inhibition both contribute to the antiproliferative action of 2-deoxyglucose in breast cancer cells
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Published in |
Breast Cancer Research and Treatment, July 2018
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DOI | 10.1007/s10549-018-4874-z |
Pubmed ID | |
Authors |
Audrey Berthe, Marie Zaffino, Claire Muller, François Foulquier, Marine Houdou, Céline Schulz, Frédéric Bost, Elia De Fay, Sabine Mazerbourg, Stéphane Flament |
Abstract |
Cancer cells often elicit a higher glycolytic rate than normal cells, supporting the development of glycolysis inhibitors as therapeutic agents. 2-Deoxyglucose (2-DG) is used in this context due to its ability to compete with glucose. However, many studies do not take into account that 2-DG inhibits not only glycolysis but also N-glycosylation. Since there are limited publications on 2-DG mechanism of action in breast cancer, we studied its effects in breast cancer cell lines to determine the part played by glycolysis inhibition and N-linked glycosylation interference. 2-Deoxyglucose behaved as an anticancer agent with a similar efficiency on cell number decrease between the hormone-dependent MCF-7 and hormone-independent MDA-MB-231 breast cancer cells. It also interfered with the N-linked glycosylation process in both cell lines as illustrated by the migration profile of the lysosomal-associated membrane protein 2 and calumenin. These results are reinforced by the appearance of an abnormal Man7GlcNAc2 structure both on lipid-linked oligosaccharides and N-linked glycoproteins of 2-DG incubated MDA-MB-231 cells. Besides, 2-DG-induced a transient endoplasmic reticulum stress that was more sustained in MDA-MB-231 cells. Both changes were abrogated by mannose. 2-DG, even in the presence of mannose, decreased glycolysis in both cell lines. Mannose partially reversed the effects of 2-DG on cell numbers with N-linked glycosylation interference accounting for 37 and 47% of 2-DG anti-cancerous effects in MDA-MB-231 and MCF-7 cells, respectively. N-linked glycosylation interference and glycolysis disruption both contribute to the anticancer properties of 2-DG in breast cancer cells. |
X Demographics
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India | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 38 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 9 | 24% |
Student > Bachelor | 7 | 18% |
Student > Master | 4 | 11% |
Researcher | 4 | 11% |
Other | 2 | 5% |
Other | 3 | 8% |
Unknown | 9 | 24% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 13 | 34% |
Agricultural and Biological Sciences | 5 | 13% |
Immunology and Microbiology | 3 | 8% |
Medicine and Dentistry | 2 | 5% |
Chemistry | 2 | 5% |
Other | 4 | 11% |
Unknown | 9 | 24% |