Blockade of the SNARE Protein Syntaxin 1 Inhibits Glioblastoma Tumor Growth

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.

Gene expression meta-analysis in diffuse low-grade glioma and the corresponding histological subtypes

“…Ulloa et al . 47 reported that inhibition of STX1A reduced glioblastoma tumour proliferation and cell invasion. In the present study, STX1A was downregulated in DLGG compared with control brain tissues.…”

Differential expression of neurogenes among breast cancer subtypes identifies high risk patients

“…Very few information is available about the role of STX1A in cancer in general or in breast cancer in particular, although it forms part of the SNARE complexes, which seem to play a role in cancer cell migration [ 73 ]. Furthermore, it was recently described that STX1A inhibition promotes glioblastoma tumor growth [ 74 ]. Moreover, in neurons, STX1A interact with netrin-1 receptors to promote chemoattraction in migrating neurons.…”

Key proteins involved in insulin vesicle exocytosis and secretion

“…Prior to formation of the SNARE complex, Sec1/Munc18 (SM) protein and Qa-SNARE binding occurred, so that the space between membranes was closed. When membrane fusion begins, the SM protein binds with the N-terminal end of the Qa-SNARE, so that it is exposed to the SNARE domain (7). First, the Qa-SNARE binds with the Qc-SNARE and Qb-SNARE to form a three element complex.…”