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

著者: Menggui Huang, Duo Zhang, Janet Y. Wu, Kun Xing, Eujin Yeo, Chunsheng Li, Lin Zhang, Eric C. Holland, Lutian Yao, Ling Qin, Zev A. Binder, Donald M. O’Rourke, Steven Brem, Constantinos Koumenis, Yanqing Gong, Yi Fan - Science Translational Medicine 2020 被引用: 139

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.