脑胶质瘤是恶性度高、危害大的神经系统原发肿瘤，目前尚无有效治疗方法。肿瘤干细胞样细胞（肿瘤起始细胞）很可能是胶质瘤发生、肿瘤异质性和复发的根源。同源异形盒转录因子PRRX1在肢体发育、实体瘤发生和转移中发挥关键作用。我们前期研究发现PRRX1反式激活多巴胺受体基因DRD2的表达，并通过其介导的p-ERK与p-AKT信号以维持脑胶质瘤干细胞样细胞的自我更新和成瘤性。本项目将系统探索PRRX1-DRD2轴在此过程中发挥功能的具体分子生物学和细胞生物学机制与意义：将在胶质瘤动物模型中应用谱系追踪方法进一步证实PRRX1是肿瘤起始细胞的标记分子；研究PRRX1和DRD2高表达的肿瘤细胞是否具有全面的干性特征；并深入阐明PRRX1促进肿瘤起始细胞自我更新的分子机制；探索在胶质瘤发生过程中阻断DRD2信号通路是否能显著抑制肿瘤的生长并改善生存率。上述研究能为开发脑胶质瘤新的治疗方法奠定基础。

Gliomas are highly aggressive and lethal primary brain tumors with limited therapeutic means. Glioma stem-like cells/glioma initiating cells (GSCs/GICs) might be responsible for tumorigenesis, heterogeneity and relapse of gliomas. Homeodomain transcription factor PRRX1 promotes GSCs/GICs’ self-renewal and tumorgenicity by inducing expression of dopamine D2 receptor, which in turn activates the p-ERK and p-AKT pro-survival signaling. This study will further explore the detail process and mechanisms how the PRRX1-DRD2 axis exerts this role. Applying lineage-tracing strategies in glioma mouse models will unveil if PRRX1 is indeed a biomarker for glioma-initiating cells. Stem-like features in Glioma cells enriched for PRRX1 and/or DRD2 and the detailed molecular mechanisms how PRRX1 promotes GICs’ self-renewal would be also explored. Furthermore, we will study if blocking DRD2 signaling would inhibit glioma growth and extend survival in glioma mouse models. This study has significance in developing means to treat gliomas.