Blockade of the SNARE Protein Syntaxin 1 Inhibits Glioblastoma Tumor Growth

• Published in: PloS 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
• Language: English
• Published: United States Public Library of Science 24.03.2015; Public Library of Science (PLoS)
• Subjects: 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; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0119707

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.