Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth

PLoS One. 2015 Mar 24;10(3):e0119707. doi: 10.1371/journal.pone.0119707. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Botulinum Toxins / pharmacology*
  • Bromodeoxyuridine
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Flow Cytometry
  • Glioblastoma / drug therapy
  • Glioblastoma / physiopathology*
  • Humans
  • Lentivirus
  • Mice
  • Neoplasm Invasiveness / prevention & control
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology*
  • Statistics, Nonparametric
  • Syntaxin 1 / antagonists & inhibitors*
  • Transduction, Genetic / methods

Substances

  • RNA, Small Interfering
  • Syntaxin 1
  • Botulinum Toxins
  • Bromodeoxyuridine

Grants and funding

FU was supported by: BFU2010-21507 (Ministerio de Economía y Competitividad (MINECO)) (www.mineco.gob.es). ES was supported by: SAF2013-42445-R (Ministerio de Economía y Competitividad (MINECO)) (www.mineco.gob.es); BFU2008-3870 (Ministerio de Economía y Competitividad (MINECO)) (www.mineco.gob.es). JS was supported by: FIS PI13/02661 (Instituto de Salud Carlos III (ISCIII)) (www.isciii.es); Asociación Española Contra el Cáncer (AECC) (www.aecc.es); and Fundación Steiner. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.