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 proteins mediate membrane fusion events in cells and are essential for many cellular processes including exocytosis and n...

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Published inPloS one Vol. 10; no. 3; p. e0119707
Main Authors Ulloa, Fausto, Gonzàlez-Juncà, Alba, Meffre, Delphine, Barrecheguren, Pablo José, Martínez-Mármol, Ramón, Pazos, Irene, Olivé, Núria, Cotrufo, Tiziana, Seoane, Joan, Soriano, Eduardo
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 24.03.2015
Public Library of Science (PLoS)
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Online AccessGet full text
ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0119707

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Abstract 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 proteins mediate membrane fusion events in cells and are essential for many cellular processes 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. Interestingly, 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.
AbstractList 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 proteins mediate membrane fusion events in cells and are essential for many cellular processes 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. Interestingly, 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.
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.
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 proteins mediate membrane fusion events in cells and are essential for many cellular processes 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. Interestingly, 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.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 proteins mediate membrane fusion events in cells and are essential for many cellular processes 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. Interestingly, 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.
Audience Academic
Author Cotrufo, Tiziana
Barrecheguren, Pablo José
Martínez-Mármol, Ramón
Pazos, Irene
Seoane, Joan
Soriano, Eduardo
Gonzàlez-Juncà, Alba
Meffre, Delphine
Olivé, Núria
Ulloa, Fausto
AuthorAffiliation 3 Translational Research Program, Vall d'Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 08035, Barcelona, Spain
5 Institute for Research in Biomedicine (IRB), Cell and Developmental Biology Program, Barcelona, 08028, Spain
6 Vall d´Hebron Institute of Research (VHIR), 08035, Barcelona, Spain
1 Department of Cell Biology, University of Barcelona, Parc Cientific de Barcelona, 08028, Barcelona, Spain
2 Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, 28031, Madrid, Spain
Swedish Neuroscience Institute, UNITED STATES
4 Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain
7 Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010, Barcelona, Spain
AuthorAffiliation_xml – name: 3 Translational Research Program, Vall d'Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital, 08035, Barcelona, Spain
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2015 Ulloa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: ES JS FU. Performed the experiments: FU AG DM PB RM IP NO TC. Analyzed the data: FU AG DM PB RM IP NO TC JS ES. Contributed reagents/materials/analysis tools: FU AG DM PB RM IP NO TC JS ES. Wrote the paper: ES JS FU.
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Snippet 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...
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StartPage e0119707
SubjectTerms Animals
Biology
Blotting, Western
Botulinum toxin
Botulinum Toxins - pharmacology
Brain
Brain cancer
Brain research
Brain tumors
Bromodeoxyuridine
Cancer treatment
Cell Line, Tumor
Cell migration
Cell proliferation
Cell Proliferation - drug effects
Cognitive science
Cytoskeletal proteins
Exocytosis
Flow Cytometry
Glioblastoma
Glioblastoma - drug therapy
Glioblastoma - physiopathology
Glioblastomas
Glioma
Gliomas
Growth
Humans
Invasiveness
Lentivirus
Membrane fusion
Mice
Neoplasm Invasiveness - prevention & control
Nervous system
Neuroscience
Neurotransmission
Proteins
Proteïnes citosquelètiques
RNA, Small Interfering - genetics
RNA, Small Interfering - pharmacology
SNAP receptors
Statistics, Nonparametric
Syntaxin
Syntaxin 1
Syntaxin 1 - antagonists & inhibitors
Toxins
Transduction, Genetic - methods
Tumors
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Title Blockade of the SNARE Protein Syntaxin 1 Inhibits Glioblastoma Tumor Growth
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