Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma

Autores
Cuello, Héctor Adrián; Ferreira, Gretel Magalí; Gulino, Cynthia Antonella; Gomez Toledo, Alejandro; Segatori, Valeria Inés; Gabri, Mariano Rolando
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Gliomas are the most common intracranial primary tumors, for which very few therapeutic options are available. The most malignant subtype is the glioblastoma, a disease associated with a 5-year survival rate lower than 5%. Given that research in glycobiology continues highlighting the role of glycans in tumor cell biology, it offers an interesting niche for the search of new therapeutic targets. In this study, we characterized aberrant glycosylation and its impact on cell biology over a broad panel of high- and low-grade glioma cell lines. Results show high expression of terminal Lewis glycans, mainly SLex, and overexpression of sialyl- and fucosyltransferases involved in their biosynthesis in high-grade glioma cell lines. Moreover, we report an association of complex multi-antennary N-glycans presenting β1,6-GlcNAc branches with the high-grade glioma cells, which also overexpressed the gene responsible for these assemblies, MGAT5. In addition, downmodulation of N-glycosylation by treatment with the inhibitors Tunicamycin/Swainsonine or MGAT5 silencing decreased SLex expression, adhesion and migration in high-grade glioma cells. In contrast, no significant changes in these cell capacities were observed in low-grade glioma after treatment with the N-glycosylation inhibitors. Furthermore, inhibition of histone deacetylases by Trichostatin A provoked an increase in the expression of SLex and its biosynthetic related glycosyltransferases in low-grade glioma cells. Our results describe that aggressive glioma cells show high expression of Lewis glycans anchored to complex multi-antennary N-glycans. This glycophenotype plays a key role in malignant cell behavior and is regulated by histone acetylation dependent mechanisms.
Fil: Cuello, Héctor Adrián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferreira, Gretel Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes; Argentina
Fil: Gomez Toledo, Alejandro. Lund University; Suecia
Fil: Segatori, Valeria Inés. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Materia
GLIOBLASTOMA
GLIOMA
HISTONE ACETYLATION
LEWIS GLYCANS
N-GLYCANS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/173340
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/173340
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade gliomaCuello, Héctor AdriánFerreira, Gretel MagalíGulino, Cynthia AntonellaGomez Toledo, AlejandroSegatori, Valeria InésGabri, Mariano RolandoGLIOBLASTOMAGLIOMAHISTONE ACETYLATIONLEWIS GLYCANSN-GLYCANShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Gliomas are the most common intracranial primary tumors, for which very few therapeutic options are available. The most malignant subtype is the glioblastoma, a disease associated with a 5-year survival rate lower than 5%. Given that research in glycobiology continues highlighting the role of glycans in tumor cell biology, it offers an interesting niche for the search of new therapeutic targets. In this study, we characterized aberrant glycosylation and its impact on cell biology over a broad panel of high- and low-grade glioma cell lines. Results show high expression of terminal Lewis glycans, mainly SLex, and overexpression of sialyl- and fucosyltransferases involved in their biosynthesis in high-grade glioma cell lines. Moreover, we report an association of complex multi-antennary N-glycans presenting β1,6-GlcNAc branches with the high-grade glioma cells, which also overexpressed the gene responsible for these assemblies, MGAT5. In addition, downmodulation of N-glycosylation by treatment with the inhibitors Tunicamycin/Swainsonine or MGAT5 silencing decreased SLex expression, adhesion and migration in high-grade glioma cells. In contrast, no significant changes in these cell capacities were observed in low-grade glioma after treatment with the N-glycosylation inhibitors. Furthermore, inhibition of histone deacetylases by Trichostatin A provoked an increase in the expression of SLex and its biosynthetic related glycosyltransferases in low-grade glioma cells. Our results describe that aggressive glioma cells show high expression of Lewis glycans anchored to complex multi-antennary N-glycans. This glycophenotype plays a key role in malignant cell behavior and is regulated by histone acetylation dependent mechanisms.Fil: Cuello, Héctor Adrián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferreira, Gretel Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaFil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes; ArgentinaFil: Gomez Toledo, Alejandro. Lund University; SueciaFil: Segatori, Valeria Inés. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; ArgentinaImpact Journals2020-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/173340Cuello, Héctor Adrián; Ferreira, Gretel Magalí; Gulino, Cynthia Antonella; Gomez Toledo, Alejandro; Segatori, Valeria Inés; et al.; Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma; Impact Journals; Oncotarget; 11; 52; 12-2020; 4822-48351949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/27850/info:eu-repo/semantics/altIdentifier/doi/10.18632/ONCOTARGET.27850info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:39Zoai:ri.conicet.gov.ar:11336/173340instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:59:39.494CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma
title Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma
spellingShingle Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma
Cuello, Héctor Adrián
GLIOBLASTOMA
GLIOMA
HISTONE ACETYLATION
LEWIS GLYCANS
N-GLYCANS
title_short Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma
title_full Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma
title_fullStr Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma
title_full_unstemmed Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma
title_sort Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma
dc.creator.none.fl_str_mv Cuello, Héctor Adrián
Ferreira, Gretel Magalí
Gulino, Cynthia Antonella
Gomez Toledo, Alejandro
Segatori, Valeria Inés
Gabri, Mariano Rolando
author Cuello, Héctor Adrián
author_facet Cuello, Héctor Adrián
Ferreira, Gretel Magalí
Gulino, Cynthia Antonella
Gomez Toledo, Alejandro
Segatori, Valeria Inés
Gabri, Mariano Rolando
author_role author
author2 Ferreira, Gretel Magalí
Gulino, Cynthia Antonella
Gomez Toledo, Alejandro
Segatori, Valeria Inés
Gabri, Mariano Rolando
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv GLIOBLASTOMA
GLIOMA
HISTONE ACETYLATION
LEWIS GLYCANS
N-GLYCANS
topic GLIOBLASTOMA
GLIOMA
HISTONE ACETYLATION
LEWIS GLYCANS
N-GLYCANS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Gliomas are the most common intracranial primary tumors, for which very few therapeutic options are available. The most malignant subtype is the glioblastoma, a disease associated with a 5-year survival rate lower than 5%. Given that research in glycobiology continues highlighting the role of glycans in tumor cell biology, it offers an interesting niche for the search of new therapeutic targets. In this study, we characterized aberrant glycosylation and its impact on cell biology over a broad panel of high- and low-grade glioma cell lines. Results show high expression of terminal Lewis glycans, mainly SLex, and overexpression of sialyl- and fucosyltransferases involved in their biosynthesis in high-grade glioma cell lines. Moreover, we report an association of complex multi-antennary N-glycans presenting β1,6-GlcNAc branches with the high-grade glioma cells, which also overexpressed the gene responsible for these assemblies, MGAT5. In addition, downmodulation of N-glycosylation by treatment with the inhibitors Tunicamycin/Swainsonine or MGAT5 silencing decreased SLex expression, adhesion and migration in high-grade glioma cells. In contrast, no significant changes in these cell capacities were observed in low-grade glioma after treatment with the N-glycosylation inhibitors. Furthermore, inhibition of histone deacetylases by Trichostatin A provoked an increase in the expression of SLex and its biosynthetic related glycosyltransferases in low-grade glioma cells. Our results describe that aggressive glioma cells show high expression of Lewis glycans anchored to complex multi-antennary N-glycans. This glycophenotype plays a key role in malignant cell behavior and is regulated by histone acetylation dependent mechanisms.
Fil: Cuello, Héctor Adrián. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferreira, Gretel Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
Fil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes; Argentina
Fil: Gomez Toledo, Alejandro. Lund University; Suecia
Fil: Segatori, Valeria Inés. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes; Argentina
description Gliomas are the most common intracranial primary tumors, for which very few therapeutic options are available. The most malignant subtype is the glioblastoma, a disease associated with a 5-year survival rate lower than 5%. Given that research in glycobiology continues highlighting the role of glycans in tumor cell biology, it offers an interesting niche for the search of new therapeutic targets. In this study, we characterized aberrant glycosylation and its impact on cell biology over a broad panel of high- and low-grade glioma cell lines. Results show high expression of terminal Lewis glycans, mainly SLex, and overexpression of sialyl- and fucosyltransferases involved in their biosynthesis in high-grade glioma cell lines. Moreover, we report an association of complex multi-antennary N-glycans presenting β1,6-GlcNAc branches with the high-grade glioma cells, which also overexpressed the gene responsible for these assemblies, MGAT5. In addition, downmodulation of N-glycosylation by treatment with the inhibitors Tunicamycin/Swainsonine or MGAT5 silencing decreased SLex expression, adhesion and migration in high-grade glioma cells. In contrast, no significant changes in these cell capacities were observed in low-grade glioma after treatment with the N-glycosylation inhibitors. Furthermore, inhibition of histone deacetylases by Trichostatin A provoked an increase in the expression of SLex and its biosynthetic related glycosyltransferases in low-grade glioma cells. Our results describe that aggressive glioma cells show high expression of Lewis glycans anchored to complex multi-antennary N-glycans. This glycophenotype plays a key role in malignant cell behavior and is regulated by histone acetylation dependent mechanisms.
publishDate 2020
dc.date.none.fl_str_mv 2020-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/173340
Cuello, Héctor Adrián; Ferreira, Gretel Magalí; Gulino, Cynthia Antonella; Gomez Toledo, Alejandro; Segatori, Valeria Inés; et al.; Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma; Impact Journals; Oncotarget; 11; 52; 12-2020; 4822-4835
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/173340
identifier_str_mv Cuello, Héctor Adrián; Ferreira, Gretel Magalí; Gulino, Cynthia Antonella; Gomez Toledo, Alejandro; Segatori, Valeria Inés; et al.; Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma; Impact Journals; Oncotarget; 11; 52; 12-2020; 4822-4835
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/27850/
info:eu-repo/semantics/altIdentifier/doi/10.18632/ONCOTARGET.27850
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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