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...

ver descrição completa

Detalhes bibliográficos
Autores: 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
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/104526
Acesso em linha:https://hdl.handle.net/2445/104526
Access Level:acceso abierto
Palavra-chave:Proteïnes citosquelètiques
Tumors
Glioma
Cytoskeletal proteins
Gliomas
Descrição
Resumo: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.