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Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth
Ulloa Darquea, Fausto Alexander; Gonzàlez Juncà, Alba; Meffre, Delphine; Barrecheguren Manero, Pablo José; Martínez Mármol, Ramón; Pazos, Irene; Olivé, Núria; Cotrufo, Tiziana; Seoane Suárez, Joan; Soriano García, Eduardo
Universitat de Barcelona
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.
Proteïnes citosquelètiques
Tumors
Glioma
Cytoskeletal proteins
Tumors
Gliomas
cc-by (c) Ulloa et al., 2015
http://creativecommons.org/licenses/by/3.0/es
Artículo
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

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