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...

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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
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2015
País:España
Recursos:Universidad de Barcelona
Repositório: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 aberto
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.