Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth

Glioblastoma (GBM) is the most prevalent adult brain tumor, with virtually no cure, and with a median overall survival of 15 months from diagnosis despite of the treatment. SNARE pro- teins mediate membrane fusion events in cells and are essential for many cellular process- es including exocytosis a...

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Authors: Ulloa Darquea, Fausto Alexander, Gonzàlez Juncà, Alba, Meffre, Delphine, Barrecheguren Manero, Pablo José, Martínez Mármol, Ramón, Pazos Capell, Irene, Olivé, Núria, Cotrufo, Tiziana, Seoane Suárez, Joan, Soriano García, Eduardo
Format: article
Status:Published version
Publication Date:2015
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/104526
Online Access:https://hdl.handle.net/2445/104526
Access Level:Open access
Keyword:Proteïnes citosquelètiques
Tumors
Glioma
Cytoskeletal proteins
Gliomas
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spelling Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growthUlloa Darquea, Fausto AlexanderGonzàlez Juncà, AlbaMeffre, DelphineBarrecheguren Manero, Pablo JoséMartínez Mármol, RamónPazos Capell, IreneOlivé, NúriaCotrufo, TizianaSeoane Suárez, JoanSoriano García, EduardoProteïnes citosquelètiquesTumorsGliomaCytoskeletal proteinsTumorsGliomasGlioblastoma (GBM) is the most prevalent adult brain tumor, with virtually no cure, and with a median overall survival of 15 months from diagnosis despite of the treatment. SNARE pro- teins mediate membrane fusion events in cells and are essential for many cellular process- es including exocytosis and neurotransmission, intracellular trafficking and cell migration. Here we show that the blockade of the SNARE protein Syntaxin 1 (Stx1) function impairs GBM cell proliferation. We show that Stx1 loss-of-function in GBM cells, through ShRNA lentiviral transduction, a Stx1 dominant negative and botulinum toxins, dramatically reduces the growth of GBM after grafting U373 cells into the brain of immune compromised mice. In- terestingly, Stx1 role on GBM progression may not be restricted just to cell proliferation since the blockade of Stx1 also reduces in vitro GBM cell invasiveness suggesting a role in several processes relevant for tumor progression. Altogether, our findings indicate that the blockade of SNARE proteins may represent a novel therapeutic tool against GBM.Public Library of Science (PLoS)2016201620152016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10 p.application/pdfhttps://hdl.handle.net/2445/104526Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0119707PLoS One, 2015, vol. 10, num. 3, p. e0119707https://doi.org/10.1371/journal.pone.0119707cc-by (c) Ulloa et al., 2015http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1045262026-05-29T05:05:01Z
dc.title.none.fl_str_mv Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth
title Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth
spellingShingle Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth
Ulloa Darquea, Fausto Alexander
Proteïnes citosquelètiques
Tumors
Glioma
Cytoskeletal proteins
Tumors
Gliomas
title_short Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth
title_full Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth
title_fullStr Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth
title_full_unstemmed Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth
title_sort Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth
dc.creator.none.fl_str_mv Ulloa Darquea, Fausto Alexander
Gonzàlez Juncà, Alba
Meffre, Delphine
Barrecheguren Manero, Pablo José
Martínez Mármol, Ramón
Pazos Capell, Irene
Olivé, Núria
Cotrufo, Tiziana
Seoane Suárez, Joan
Soriano García, Eduardo
author Ulloa Darquea, Fausto Alexander
author_facet Ulloa Darquea, Fausto Alexander
Gonzàlez Juncà, Alba
Meffre, Delphine
Barrecheguren Manero, Pablo José
Martínez Mármol, Ramón
Pazos Capell, Irene
Olivé, Núria
Cotrufo, Tiziana
Seoane Suárez, Joan
Soriano García, Eduardo
author_role author
author2 Gonzàlez Juncà, Alba
Meffre, Delphine
Barrecheguren Manero, Pablo José
Martínez Mármol, Ramón
Pazos Capell, Irene
Olivé, Núria
Cotrufo, Tiziana
Seoane Suárez, Joan
Soriano García, Eduardo
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Proteïnes citosquelètiques
Tumors
Glioma
Cytoskeletal proteins
Tumors
Gliomas
topic Proteïnes citosquelètiques
Tumors
Glioma
Cytoskeletal proteins
Tumors
Gliomas
description Glioblastoma (GBM) is the most prevalent adult brain tumor, with virtually no cure, and with a median overall survival of 15 months from diagnosis despite of the treatment. SNARE pro- teins mediate membrane fusion events in cells and are essential for many cellular process- es including exocytosis and neurotransmission, intracellular trafficking and cell migration. Here we show that the blockade of the SNARE protein Syntaxin 1 (Stx1) function impairs GBM cell proliferation. We show that Stx1 loss-of-function in GBM cells, through ShRNA lentiviral transduction, a Stx1 dominant negative and botulinum toxins, dramatically reduces the growth of GBM after grafting U373 cells into the brain of immune compromised mice. In- terestingly, Stx1 role on GBM progression may not be restricted just to cell proliferation since the blockade of Stx1 also reduces in vitro GBM cell invasiveness suggesting a role in several processes relevant for tumor progression. Altogether, our findings indicate that the blockade of SNARE proteins may represent a novel therapeutic tool against GBM.
publishDate 2015
dc.date.none.fl_str_mv 2015
2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/104526
url https://hdl.handle.net/2445/104526
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0119707
PLoS One, 2015, vol. 10, num. 3, p. e0119707
https://doi.org/10.1371/journal.pone.0119707
dc.rights.none.fl_str_mv cc-by (c) Ulloa et al., 2015
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ulloa et al., 2015
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869423866694074368
score 15.198674

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