English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Therapeutic resistance remains a persistent challenge for patients with glioblastoma (GBM). Here, we report that endothelial cells (ECs) acquire transformation into mesenchymal stem cell (MSC)-like cells in GBM, driving tumor resistance to cytotoxic treatment. Single-cell transcriptome analysis identified an EC-derived cell population that robustly expresses mesenchymal genes and stem cell-associated markers, suggesting that ECs undergo mesenchymal transformation and stemness-like activation in GBM microenvironment. Furthermore, we identified a c-Met-mediated axis that induces β-catenin phosphorylation at Ser675 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.

TAMI-26. SINGLE-CELL TRANSCRIPTOME ANALYSIS REVEALS THAT ENDOTHELIAL TRANSFORMATION DRIVES GLIOBLASTOMA CHEMORESISTANCE VIA Wnt/β-CATENIN/MRP-1