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UGCG influences glutamine metabolism of breast cancer cells

UDP-glucose ceramide glucosyltransferase (UGCG) is the key enzyme in glycosphingolipid (GSL) metabolism by being the only enzyme that generates glucosylceramide (GlcCer) de novo. Increased UGCG synthesis is associated with pro-cancerous processes such as increased proliferation and multidrug resista...

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Autores principales: Schömel, Nina, Hancock, Sarah E., Gruber, Lisa, Olzomer, Ellen M., Byrne, Frances L., Shah, Divya, Hoehn, Kyle L., Turner, Nigel, Grösch, Sabine, Geisslinger, Gerd, Wegner, Marthe-Susanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821892/
https://www.ncbi.nlm.nih.gov/pubmed/31666638
http://dx.doi.org/10.1038/s41598-019-52169-7
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author Schömel, Nina
Hancock, Sarah E.
Gruber, Lisa
Olzomer, Ellen M.
Byrne, Frances L.
Shah, Divya
Hoehn, Kyle L.
Turner, Nigel
Grösch, Sabine
Geisslinger, Gerd
Wegner, Marthe-Susanna
author_facet Schömel, Nina
Hancock, Sarah E.
Gruber, Lisa
Olzomer, Ellen M.
Byrne, Frances L.
Shah, Divya
Hoehn, Kyle L.
Turner, Nigel
Grösch, Sabine
Geisslinger, Gerd
Wegner, Marthe-Susanna
author_sort Schömel, Nina
collection PubMed
description UDP-glucose ceramide glucosyltransferase (UGCG) is the key enzyme in glycosphingolipid (GSL) metabolism by being the only enzyme that generates glucosylceramide (GlcCer) de novo. Increased UGCG synthesis is associated with pro-cancerous processes such as increased proliferation and multidrug resistance in several cancer types. We investigated the influence of UGCG overexpression on glutamine metabolism in breast cancer cells. We observed adapted glucose and glutamine uptake in a limited energy supply environment following UGCG overexpression. Glutamine is used for reinforced oxidative stress response shown by increased mRNA expression of glutamine metabolizing proteins such as glutathione-disulfide reductase (GSR) resulting in increased reduced glutathione (GSH) level. Augmented glutamine uptake is also used for fueling the tricarboxylic acid (TCA) cycle to maintain the proliferative advantage of UGCG overexpressing cells. Our data reveal a link between GSL and glutamine metabolism in breast cancer cells, which is to our knowledge a novel correlation in the field of sphingolipid research.
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spelling pubmed-68218922019-11-05 UGCG influences glutamine metabolism of breast cancer cells Schömel, Nina Hancock, Sarah E. Gruber, Lisa Olzomer, Ellen M. Byrne, Frances L. Shah, Divya Hoehn, Kyle L. Turner, Nigel Grösch, Sabine Geisslinger, Gerd Wegner, Marthe-Susanna Sci Rep Article UDP-glucose ceramide glucosyltransferase (UGCG) is the key enzyme in glycosphingolipid (GSL) metabolism by being the only enzyme that generates glucosylceramide (GlcCer) de novo. Increased UGCG synthesis is associated with pro-cancerous processes such as increased proliferation and multidrug resistance in several cancer types. We investigated the influence of UGCG overexpression on glutamine metabolism in breast cancer cells. We observed adapted glucose and glutamine uptake in a limited energy supply environment following UGCG overexpression. Glutamine is used for reinforced oxidative stress response shown by increased mRNA expression of glutamine metabolizing proteins such as glutathione-disulfide reductase (GSR) resulting in increased reduced glutathione (GSH) level. Augmented glutamine uptake is also used for fueling the tricarboxylic acid (TCA) cycle to maintain the proliferative advantage of UGCG overexpressing cells. Our data reveal a link between GSL and glutamine metabolism in breast cancer cells, which is to our knowledge a novel correlation in the field of sphingolipid research. Nature Publishing Group UK 2019-10-30 /pmc/articles/PMC6821892/ /pubmed/31666638 http://dx.doi.org/10.1038/s41598-019-52169-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Schömel, Nina
Hancock, Sarah E.
Gruber, Lisa
Olzomer, Ellen M.
Byrne, Frances L.
Shah, Divya
Hoehn, Kyle L.
Turner, Nigel
Grösch, Sabine
Geisslinger, Gerd
Wegner, Marthe-Susanna
UGCG influences glutamine metabolism of breast cancer cells
title UGCG influences glutamine metabolism of breast cancer cells
title_full UGCG influences glutamine metabolism of breast cancer cells
title_fullStr UGCG influences glutamine metabolism of breast cancer cells
title_full_unstemmed UGCG influences glutamine metabolism of breast cancer cells
title_short UGCG influences glutamine metabolism of breast cancer cells
title_sort ugcg influences glutamine metabolism of breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821892/
https://www.ncbi.nlm.nih.gov/pubmed/31666638
http://dx.doi.org/10.1038/s41598-019-52169-7
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