Vulnerability of invasive glioblastoma cells to lysosomal membrane destabilisation

ABSTRACT: The current clinical care of glioblastomas leaves behind invasive, radio- and chemo-resistant cells. We recently identified mammary-derived growth inhibitor (MDGI/FABP3) as a biomarker for invasive gliomas. Here, we demonstrate a novel function for MDGI in the maintenance of lysosomal membrane integrity, thus rendering invasive glioma cells unexpectedly vulnerable to lysosomal membrane destabilisation. MDGI silencing impaired trafficking of polyunsaturated fatty acids into cells resulting in significant alterations in the lipid composition of lysosomal membranes, and subsequent death of the patient-derived glioma cells via lysosomal membrane permeabilization (LMP). In a preclinical model, treatment of glioma-bearing mice with an anti-histaminergic LMP-inducing drug efficiently eradicated i

SUBMITTER: Dr. Vadim Le Joncour 

PROVIDER: S-SCDT-EMM-2018-09034 | biostudies-other |

REPOSITORIES: biostudies-other