恶性胶质瘤EGFR过表达经常伴随EGFRvIII的突变。表达EGFRvIII的胶质瘤细胞促进IL-6自分泌，维持肿瘤"干性"微环境，启动胶质瘤的发生和维持其肿瘤干细胞的特性。我们前期研究发现，胶质瘤细胞发生EGFRvIII细胞核转位，过表达CD133激活Erk磷酸化。在本项目中，我们将研究EGFR/EGFRvIII如何通过Ras/Erk磷酸化途径活化细胞经典信号通路，或经EGFR/EGFRvIII细胞核转位介导C/EBP-β的转录活性，上调胶质瘤"干性"基因CD133的表达, 协同JAKs/STAT3促进IL-6的自分泌？进一步研究CD133的表达，如何通过胶质瘤细胞膜ADAMS介导EGFR配体分子如TGFs的剪切，激活Erk磷酸化，正反馈增强C/EBP-β介导的胶质瘤"干性"的分子表达和"干性"微环境的维持? C/EBP-β作为重要的转录因子介导胶质瘤的发生和发展，可能是新的治疗靶点。

EGFRvIII mutation occurs frequent associated with EGFR overexpression in malignant glioma. Glioma cells expressing EGFRvIII promote autocrine IL-6 and cancer stem cells (GSC)-initiated glioma to maintain "stemness" niche and properties. Our previous study found that EGFRvIII located in the nucleus of glioma cells and involved in EGFRvIII nuclear translocation. Overexpression of CD133 promotes the phosphorylation of Erk in glioblastoma cells. Our project will study that how to stimulate EGFR/EGFRvIII and Ras/Erk phosphorylation by activation of classic cell signaling pathways, or by the EGFR/EGFRvIII nuclear translocation, mediated by C/EBP-β transcriptional activity, increase "stemness" CD133 gene expression, and cross-talk with JAKs/STAT3 promote IL-6 autosecretion. CD133 expression how to be with cell membrane ADAMS mediated by EGFR ligands such as TGFs splice variants, activate phosphorylation of Erk, promote positive feedback to enhance C/EBP-β mediated "stemness" gene expression and micro-environment maintenance. In malignant glioma C/EBP-β as an important transcription factor mediated development and progression has provided new therapeutic targets.