Wnt-mediated endothelial transformation into mesenchymal stem cell–like cells induces chemoresistance in glioblastoma

Abstract

and Wnt signaling activation, inducing multidrug resistance-associated protein-1(MRP-1) expression and leading to EC stemness-like activation and chemoresistance. Last, genetic ablation of β-catenin in ECs overcome GBM tumor resistance to temozolomide (TMZ) chemotherapy in vivo. Combination of Wnt inhibition and TMZ chemotherapy eliminated tumor-associated ECs, inhibited GBM growth, and increased mouse survival. These findings identified a cell plasticity-based, microenvironment-dependent mechanism that controls tumor chemoresistance, and suggest that targeting Wnt/β-catenin-mediated EC transformation and stemness activation may overcome therapeutic resistance in GBM.