N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma

Autores
Ferreira, Gretel Magalí; Cuello, Héctor Adrián; Nogueira, Aylen Camila; Castillo, Jeremias Omar; Rojo, Selene; Gulino, Cynthia Antonella; Segatori, Valeria Inés; Gabri, Mariano Rolando
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Integrin αV (IαV) and the urokinase-type plasminogen activator receptor (uPAR) are key mediators of tumor malignancy in Glioblastoma. This study aims to characterize IαV/uPAR interaction in GBM and investigate the role played by glycans in this scenario. Protein expression and interaction were confirmed via confocal microscopy and co-immunoprecipitation. The role of N-glycosylation was evaluated using Swainsonine (SW) and PNGase F. IαV glycoproteomic analysis was performed by mass spectrometry. Sialic acids and glycan structures in IαV/uPAR interaction were tested using neuraminidase A (NeuA) and lectin interference assays, respectively. Protein expression and their interaction were detected in GBM cells, but not in low-grade glioma cells, even in cells transfected to overexpress uPAR. SW, PNGase, and NeuA treatments significantly reduced IαV/uPAR interaction. Also, lectin interference assays indicated that β1-6 branched glycans play a crucial role in this interaction. Analysis of the IαV glycosylation profile revealed the presence of complex and hybrid N-glycans in GBM, while only oligomannose N-glycans were identified in low-grade glioma. N-glycosylation inhibition and sialic acid removal reduced AKT phosphorylation. Our findings demonstrate, for the first time, the interaction between IαV and uPAR in GBM cells, highlighting the essential role of N-glycosylation, particularly β1-6 branched glycans and sialic acids.
Fil: Ferreira, Gretel Magalí. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cuello, Héctor Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Nogueira, Aylen Camila. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Castillo, Jeremias Omar. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rojo, Selene. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Materia
IaV
uPAR
N-glycosylation
Sialic acid
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/281760
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in GlioblastomaFerreira, Gretel MagalíCuello, Héctor AdriánNogueira, Aylen CamilaCastillo, Jeremias OmarRojo, SeleneGulino, Cynthia AntonellaSegatori, Valeria InésGabri, Mariano RolandoIaVuPARN-glycosylationSialic acidhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Integrin αV (IαV) and the urokinase-type plasminogen activator receptor (uPAR) are key mediators of tumor malignancy in Glioblastoma. This study aims to characterize IαV/uPAR interaction in GBM and investigate the role played by glycans in this scenario. Protein expression and interaction were confirmed via confocal microscopy and co-immunoprecipitation. The role of N-glycosylation was evaluated using Swainsonine (SW) and PNGase F. IαV glycoproteomic analysis was performed by mass spectrometry. Sialic acids and glycan structures in IαV/uPAR interaction were tested using neuraminidase A (NeuA) and lectin interference assays, respectively. Protein expression and their interaction were detected in GBM cells, but not in low-grade glioma cells, even in cells transfected to overexpress uPAR. SW, PNGase, and NeuA treatments significantly reduced IαV/uPAR interaction. Also, lectin interference assays indicated that β1-6 branched glycans play a crucial role in this interaction. Analysis of the IαV glycosylation profile revealed the presence of complex and hybrid N-glycans in GBM, while only oligomannose N-glycans were identified in low-grade glioma. N-glycosylation inhibition and sialic acid removal reduced AKT phosphorylation. Our findings demonstrate, for the first time, the interaction between IαV and uPAR in GBM cells, highlighting the essential role of N-glycosylation, particularly β1-6 branched glycans and sialic acids.Fil: Ferreira, Gretel Magalí. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cuello, Héctor Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Nogueira, Aylen Camila. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Castillo, Jeremias Omar. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rojo, Selene. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaMolecular Diversity Preservation International2025-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/281760Ferreira, Gretel Magalí; Cuello, Héctor Adrián; Nogueira, Aylen Camila; Castillo, Jeremias Omar; Rojo, Selene; et al.; N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 11; 5-2025; 1-171422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/26/11/5310info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms26115310info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-11T12:28:45Zoai:ri.conicet.gov.ar:11336/281760instacron: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:34982026-03-11 12:28:46.11CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma
title N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma
spellingShingle N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma
Ferreira, Gretel Magalí
IaV
uPAR
N-glycosylation
Sialic acid
title_short N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma
title_full N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma
title_fullStr N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma
title_full_unstemmed N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma
title_sort N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma
dc.creator.none.fl_str_mv Ferreira, Gretel Magalí
Cuello, Héctor Adrián
Nogueira, Aylen Camila
Castillo, Jeremias Omar
Rojo, Selene
Gulino, Cynthia Antonella
Segatori, Valeria Inés
Gabri, Mariano Rolando
author Ferreira, Gretel Magalí
author_facet Ferreira, Gretel Magalí
Cuello, Héctor Adrián
Nogueira, Aylen Camila
Castillo, Jeremias Omar
Rojo, Selene
Gulino, Cynthia Antonella
Segatori, Valeria Inés
Gabri, Mariano Rolando
author_role author
author2 Cuello, Héctor Adrián
Nogueira, Aylen Camila
Castillo, Jeremias Omar
Rojo, Selene
Gulino, Cynthia Antonella
Segatori, Valeria Inés
Gabri, Mariano Rolando
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv IaV
uPAR
N-glycosylation
Sialic acid
topic IaV
uPAR
N-glycosylation
Sialic acid
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Integrin αV (IαV) and the urokinase-type plasminogen activator receptor (uPAR) are key mediators of tumor malignancy in Glioblastoma. This study aims to characterize IαV/uPAR interaction in GBM and investigate the role played by glycans in this scenario. Protein expression and interaction were confirmed via confocal microscopy and co-immunoprecipitation. The role of N-glycosylation was evaluated using Swainsonine (SW) and PNGase F. IαV glycoproteomic analysis was performed by mass spectrometry. Sialic acids and glycan structures in IαV/uPAR interaction were tested using neuraminidase A (NeuA) and lectin interference assays, respectively. Protein expression and their interaction were detected in GBM cells, but not in low-grade glioma cells, even in cells transfected to overexpress uPAR. SW, PNGase, and NeuA treatments significantly reduced IαV/uPAR interaction. Also, lectin interference assays indicated that β1-6 branched glycans play a crucial role in this interaction. Analysis of the IαV glycosylation profile revealed the presence of complex and hybrid N-glycans in GBM, while only oligomannose N-glycans were identified in low-grade glioma. N-glycosylation inhibition and sialic acid removal reduced AKT phosphorylation. Our findings demonstrate, for the first time, the interaction between IαV and uPAR in GBM cells, highlighting the essential role of N-glycosylation, particularly β1-6 branched glycans and sialic acids.
Fil: Ferreira, Gretel Magalí. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cuello, Héctor Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Nogueira, Aylen Camila. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Castillo, Jeremias Omar. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rojo, Selene. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Segatori, Valeria Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Gabri, Mariano Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
description Integrin αV (IαV) and the urokinase-type plasminogen activator receptor (uPAR) are key mediators of tumor malignancy in Glioblastoma. This study aims to characterize IαV/uPAR interaction in GBM and investigate the role played by glycans in this scenario. Protein expression and interaction were confirmed via confocal microscopy and co-immunoprecipitation. The role of N-glycosylation was evaluated using Swainsonine (SW) and PNGase F. IαV glycoproteomic analysis was performed by mass spectrometry. Sialic acids and glycan structures in IαV/uPAR interaction were tested using neuraminidase A (NeuA) and lectin interference assays, respectively. Protein expression and their interaction were detected in GBM cells, but not in low-grade glioma cells, even in cells transfected to overexpress uPAR. SW, PNGase, and NeuA treatments significantly reduced IαV/uPAR interaction. Also, lectin interference assays indicated that β1-6 branched glycans play a crucial role in this interaction. Analysis of the IαV glycosylation profile revealed the presence of complex and hybrid N-glycans in GBM, while only oligomannose N-glycans were identified in low-grade glioma. N-glycosylation inhibition and sialic acid removal reduced AKT phosphorylation. Our findings demonstrate, for the first time, the interaction between IαV and uPAR in GBM cells, highlighting the essential role of N-glycosylation, particularly β1-6 branched glycans and sialic acids.
publishDate 2025
dc.date.none.fl_str_mv 2025-05
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/11336/281760
Ferreira, Gretel Magalí; Cuello, Héctor Adrián; Nogueira, Aylen Camila; Castillo, Jeremias Omar; Rojo, Selene; et al.; N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 11; 5-2025; 1-17
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/281760
identifier_str_mv Ferreira, Gretel Magalí; Cuello, Héctor Adrián; Nogueira, Aylen Camila; Castillo, Jeremias Omar; Rojo, Selene; et al.; N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 11; 5-2025; 1-17
1422-0067
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.mdpi.com/1422-0067/26/11/5310
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms26115310
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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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