title: Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth.
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.
authors: Department of Cell Biology, University of Barcelona, Parc Cientific de Barcelona, 08028, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, 28031, Madrid, Spain.
authors: Fausto
authors: F
authors: Ulloa
authors: Translational Research Program, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, 08035, Barcelona, Spain; Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain.
authors: Alba
authors: A
authors: Gonzàlez-Juncà
authors: Department of Cell Biology, University of Barcelona, Parc Cientific de Barcelona, 08028, Barcelona, Spain.
authors: Delphine
authors: D
authors: Meffre
authors: Department of Cell Biology, University of Barcelona, Parc Cientific de Barcelona, 08028, Barcelona, Spain; Institute for Research in Biomedicine (IRB), Cell and Developmental Biology Program, Barcelona, 08028, Spain.
authors: Pablo José
authors: PJ
authors: Barrecheguren
authors: Department of Cell Biology, University of Barcelona, Parc Cientific de Barcelona, 08028, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, 28031, Madrid, Spain.
authors: Ramón
authors: R
authors: Martínez-Mármol
authors: Department of Cell Biology, University of Barcelona, Parc Cientific de Barcelona, 08028, Barcelona, Spain.
authors: Irene
authors: I
authors: Pazos
authors: Department of Cell Biology, University of Barcelona, Parc Cientific de Barcelona, 08028, Barcelona, Spain.
authors: Núria
authors: N
authors: Olivé
authors: Department of Cell Biology, University of Barcelona, Parc Cientific de Barcelona, 08028, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, 28031, Madrid, Spain.
authors: Tiziana
authors: T
authors: Cotrufo
authors: Translational Research Program, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, 08035, Barcelona, Spain; Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010, Barcelona, Spain.
authors: Joan
authors: J
authors: Seoane
authors: Department of Cell Biology, University of Barcelona, Parc Cientific de Barcelona, 08028, Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, 28031, Madrid, Spain; Vall d´Hebron Institute of Research (VHIR), 08035, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010, Barcelona, Spain.
authors: Eduardo
authors: E
authors: Soriano
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001905:Botulinum Toxins / Q000494:pharmacology*; D001973:Bromodeoxyuridine; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D016086:Lentivirus; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D050827:Syntaxin 1 / Q000037:antagonists & inhibitors*; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D034741:RNA, Small Interfering; D050827:Syntaxin 1; D001905:Botulinum Toxins; D001973:Bromodeoxyuridine