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The glycomic effect of N-acetylglucosaminyltransferase III overexpression in metastatic melanoma cells. GnT-III modifies highly branched N-glycans

N-acetylglucosaminyltransferase III (GnT-III) is known to catalyze N-glycan “bisection” and thereby modulate the formation of highly branched complex structures within the Golgi apparatus. While active, it inhibits the action of other GlcNAc transferases such as GnT-IV and GnT-V. Moreover, GnT-III i...

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Autores principales: Link-Lenczowski, Paweł, Bubka, Monika, Balog, Crina I. A., Koeleman, Carolien A. M., Butters, Terry D., Wuhrer, Manfred, Lityńska, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916991/
https://www.ncbi.nlm.nih.gov/pubmed/29502191
http://dx.doi.org/10.1007/s10719-018-9814-y
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author Link-Lenczowski, Paweł
Bubka, Monika
Balog, Crina I. A.
Koeleman, Carolien A. M.
Butters, Terry D.
Wuhrer, Manfred
Lityńska, Anna
author_facet Link-Lenczowski, Paweł
Bubka, Monika
Balog, Crina I. A.
Koeleman, Carolien A. M.
Butters, Terry D.
Wuhrer, Manfred
Lityńska, Anna
author_sort Link-Lenczowski, Paweł
collection PubMed
description N-acetylglucosaminyltransferase III (GnT-III) is known to catalyze N-glycan “bisection” and thereby modulate the formation of highly branched complex structures within the Golgi apparatus. While active, it inhibits the action of other GlcNAc transferases such as GnT-IV and GnT-V. Moreover, GnT-III is considered as an inhibitor of the metastatic potential of cancer cells both in vitro and in vivo. However, the effects of GnT-III may be more diverse and depend on the cellular context. We describe the detailed glycomic analysis of the effect of GnT-III overexpression in WM266–4-GnT-III metastatic melanoma cells. We used MALDI-TOF and ESI-ion-trap-MS/MS together with HILIC-HPLC of 2-AA labeled N-glycans to study the N-glycome of membrane-attached and secreted proteins. We found that the overexpression of GnT-III in melanoma leads to the modification of a broad range of N-glycan types by the introduction of the “bisecting” GlcNAc residue with highly branched complex structures among them. The presence of these unusual complex N-glycans resulted in stronger interactions of cellular glycoproteins with the PHA-L. Based on the data presented here we conclude that elevated activity of GnT-III in cancer cells does not necessarily lead to a total abrogation of the formation of highly branched glycans. In addition, the modification of pre-existing N-glycans by the introduction of “bisecting” GlcNAc can modulate their capacity to interact with carbohydrate-binding proteins such as plant lectins. Our results suggest further studies on the biological function of “bisected” oligosaccharides in cancer cell biology and their interactions with carbohydrate-binding proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10719-018-9814-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-59169912018-04-30 The glycomic effect of N-acetylglucosaminyltransferase III overexpression in metastatic melanoma cells. GnT-III modifies highly branched N-glycans Link-Lenczowski, Paweł Bubka, Monika Balog, Crina I. A. Koeleman, Carolien A. M. Butters, Terry D. Wuhrer, Manfred Lityńska, Anna Glycoconj J Original Article N-acetylglucosaminyltransferase III (GnT-III) is known to catalyze N-glycan “bisection” and thereby modulate the formation of highly branched complex structures within the Golgi apparatus. While active, it inhibits the action of other GlcNAc transferases such as GnT-IV and GnT-V. Moreover, GnT-III is considered as an inhibitor of the metastatic potential of cancer cells both in vitro and in vivo. However, the effects of GnT-III may be more diverse and depend on the cellular context. We describe the detailed glycomic analysis of the effect of GnT-III overexpression in WM266–4-GnT-III metastatic melanoma cells. We used MALDI-TOF and ESI-ion-trap-MS/MS together with HILIC-HPLC of 2-AA labeled N-glycans to study the N-glycome of membrane-attached and secreted proteins. We found that the overexpression of GnT-III in melanoma leads to the modification of a broad range of N-glycan types by the introduction of the “bisecting” GlcNAc residue with highly branched complex structures among them. The presence of these unusual complex N-glycans resulted in stronger interactions of cellular glycoproteins with the PHA-L. Based on the data presented here we conclude that elevated activity of GnT-III in cancer cells does not necessarily lead to a total abrogation of the formation of highly branched glycans. In addition, the modification of pre-existing N-glycans by the introduction of “bisecting” GlcNAc can modulate their capacity to interact with carbohydrate-binding proteins such as plant lectins. Our results suggest further studies on the biological function of “bisected” oligosaccharides in cancer cell biology and their interactions with carbohydrate-binding proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10719-018-9814-y) contains supplementary material, which is available to authorized users. Springer US 2018-03-03 2018 /pmc/articles/PMC5916991/ /pubmed/29502191 http://dx.doi.org/10.1007/s10719-018-9814-y Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
spellingShingle Original Article
Link-Lenczowski, Paweł
Bubka, Monika
Balog, Crina I. A.
Koeleman, Carolien A. M.
Butters, Terry D.
Wuhrer, Manfred
Lityńska, Anna
The glycomic effect of N-acetylglucosaminyltransferase III overexpression in metastatic melanoma cells. GnT-III modifies highly branched N-glycans
title The glycomic effect of N-acetylglucosaminyltransferase III overexpression in metastatic melanoma cells. GnT-III modifies highly branched N-glycans
title_full The glycomic effect of N-acetylglucosaminyltransferase III overexpression in metastatic melanoma cells. GnT-III modifies highly branched N-glycans
title_fullStr The glycomic effect of N-acetylglucosaminyltransferase III overexpression in metastatic melanoma cells. GnT-III modifies highly branched N-glycans
title_full_unstemmed The glycomic effect of N-acetylglucosaminyltransferase III overexpression in metastatic melanoma cells. GnT-III modifies highly branched N-glycans
title_short The glycomic effect of N-acetylglucosaminyltransferase III overexpression in metastatic melanoma cells. GnT-III modifies highly branched N-glycans
title_sort glycomic effect of n-acetylglucosaminyltransferase iii overexpression in metastatic melanoma cells. gnt-iii modifies highly branched n-glycans
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916991/
https://www.ncbi.nlm.nih.gov/pubmed/29502191
http://dx.doi.org/10.1007/s10719-018-9814-y
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