Spy1/CLIPR-59相互作用对胶质瘤凋亡和侵袭性的影响及其机制

胶质瘤是中枢神经系统最常见的恶性肿瘤，具高度侵袭性生长的特性。本课题组的前期研究发现Spy1在胶质瘤中表达异常，与胶质瘤的分级和恶性程度正相关。为了研究其在胶质瘤中的功能，课题组通过酵母双杂交分析发现胶质瘤微环境信号通路中重要的调节分子CLIPR-59与Spy1存在相互作用。基于此，我们假设在胶质瘤中高水平的Spy1与CLIPR-59相结合，抑制了TNF-α诱导的凋亡作用，相反促进了胶质瘤细胞的迁移和侵袭性。因此，本课题拟在细胞水平分析Spy1与CLIPR-59的相互作用及其对下游信号途径以及胶质瘤细胞增殖、迁移及侵袭的生物学影响；同时结合临床资料分析Spy1与CLIPR-59作用与胶质瘤发生及预后的关系；最后运用裸鼠脑内胶质瘤模型，分析干预Spy1与CLIPR-59对胶质瘤发生及侵袭的影响。课题的完成将有助于揭示胶质瘤微环境对胶质瘤发生的影响，为胶质瘤的治疗提供新的靶点。

Gliomas are the most frequent primary brain tumors. The highly lethal nature of this tumor results from the acquisition of an invasive phenotype that allows the tumor cells to infiltrate the surrounding brain tissue of an invasive phenotype.According to the previous study,we found that in malignant gliomas Spy1 is frequently overexpressed and critically regulates the proliferation of glioma cells.A malignant glioma phenotype is associated with higher Spy1 expression, as opposed to Spy1 expression in normal brain tissue or a more benign glioma phenotype.To further delineate the role of Spy1 in glioma Spy1,we identified CLIPR-59 as a novel interacting protein for Spy1 by yeast two hybrid (Y2H) screening,playing an important role in glioma unique microenvironment.Terefore,we hypothesized that Spy1 overexpression suppressed TNF-α-mediated apoptosis and promoted the migration and invasion of glioma cells through the interaction with CLIPR-59. Therefore, our group aimed to analyze the interaction of Spy1 and CLIPR-59 and the downstream signaling pathways, as well as the biological behavior of glioma proliferation, migration and invasiveness at the cellular level.At the same time,to analyze the role of Spy1 and CLIPR-59 combined with the clinical data in glioma.Finally, using the brain of nude mice to build glioma model and analyzing effect of interference of the interaction of Spy1 and CLIPR-59 on the development and invasion of glioma.