Title :

Protein N-glycosylation alteration and glycolysis inhibition both contribute to the antiproliferative action of 2-deoxyglucose in breast cancer cells

Author(s) :

Berthe, Audrey [Auteur]
Centre de Recherche en Automatique de Nancy [CRAN]
Zaffino, Marie [Auteur]
Centre de Recherche en Automatique de Nancy [CRAN]
Muller, Claire [Auteur]
Centre de Recherche en Automatique de Nancy [CRAN]
Foulquier, Francois [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Houdou, Marine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576
Schulz, Celine [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Bost, Frédéric [Auteur]
Centre méditerranéen de médecine moléculaire [C3M]
De Fay, Elia [Auteur]
Centre de Recherche en Automatique de Nancy [CRAN]
Mazerbourg, Sabine [Auteur]
Centre de Recherche en Automatique de Nancy [CRAN]
Flament, Stéphane [Auteur]
Centre de Recherche en Automatique de Nancy [CRAN]

Journal title :

Breast cancer research and treatment

Volume number :

171

Pages :

581-591

Publication date :

2018-07-03

ISSN :

0167-6806, 1573-7217

English keyword(s) :

Breast cancer
2-Deoxyglucose
Glycolysis
N-Glycosylation
Endoplasmic reticulum stress

HAL domain(s) :

Chimie/Chimie théorique et/ou physique

English abstract : [en]

Purpose : 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 ...
Show more >Purpose : 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. Methods and Results : 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. Conclusion : N-linked glycosylation interference and glycolysis disruption both contribute to the anticancer properties of 2-DG in breast cancer cells.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CNRS
Université de Lille

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Mécanismes moléculaires de la N-glycosylation et pathologies associées
Chemical Glycobiology

Submission date :

2020-02-12T15:45:38Z
2021-06-10T16:26:41Z
2024-02-23T09:17:35Z