胶质瘤是最主要的恶性神经系统肿瘤，上皮-间质转化（EMT）是调节胶质瘤生物学的主要调控方式之一，但缺乏EMT调节胶质瘤发生的分子机制研究。我们前期发现血小板衍生因子受体（PDGFR alpha）是调节胶质瘤增殖与侵袭的关键驱动因子；对临床大数据分析表明ZEB1和PDGFRA共表达；PDGF-A刺激，促进ZEB1转录上调和磷酸化；敲除ZEB1抑制了PDGFR alpha驱动的胶质瘤的EMT。并且，比较多个胶质瘤干细胞和肿瘤细胞，结果表明EMT家族中的ZEB1特异的在肿瘤干细胞中高表达；敲除ZEB1降低肿瘤干细胞的克隆形成。本项目将深入揭示ZEB1及其磷酸化参与调节胶质瘤EMT和干细胞干性的分子机制，同时，结合临床样本，分析ZEB1的临床应用价值，探讨干扰ZEB1敏化放疗的方法。该研究的顺利完成，不仅有助于揭示ZEB1调节胶质瘤发生的分子机制，而且将为临床疾病预测和治疗提供坚实的理论基础。

Gliomablstoma is the most malignant tumor in central neuron system, and epithelial-mesenchymal transition (EMT) is one of key ways to mediate gliomagenesis. However, the mechanisms of EMT-regulated gliomagenesis are still elusive. Previous we and others found that PDGFR alpha is a main driver of glioma proliferation and invasion. We also found that ZEB1 and PDGFRA co-expression in clinical specimens by Meta-data analysis, and PDGF-A stimulation promoted ZEB1 transcription and phosphorylation. Morevoer, knockdown of ZEB1 inhibited PDGFR alpha-driven glioma proliferation and EMT. Most interestingly, compared gene expression differentiation between in various glioma stem cells and in various glioma cells, it was shown that ZEB1, a member of EMT-related protein family, was highly and specifically expressed in glioma stem cells. Depletion of ZEB1 significantly decreased the colony formation of glioma stem cells. Our project will deeply explore the mechanisms of ZEB1-regulated glioma EMT and glioma stem cell stemness. Binding with clinical specimen analysis, we will also address the roles of ZEB1 in clinical treatment and tumor radioresistance. This will help not only to understand the molecular mechanisms of ZEB1-mediated gliomagenesis, but also to provide potential research basis for clinical diagnosis and therapy.