Cbx7调控Hippo信号通路影响脑恶性胶质瘤侵袭、迁移过程的机制研究

Hippo 通路是新发现的可调节细胞侵袭/迁移的蛋白激酶通路，其失调与肿瘤的恶性进展密切相关，但其上游调控机制缺乏研究。虽然Cbx7在人类多种肿瘤被发现具有抑制肿瘤进展的作用，但目前其具体机制尚未阐明。基于我们初步发现Cbx7有抑制脑胶质瘤细胞侵袭/迁移及激活 Hippo 通路的作用，本项目拟以脑胶质瘤标本，培养的细胞及裸鼠为研究对象，以调节细胞侵袭/迁移的 Hippo 通路为切入点，从分子、细胞与整体水平研究Cbx7对脑胶质瘤细胞进展（侵袭/迁移）的影响；Cbx7对 Hippo 通路关键蛋白的水平与活性的调节；阐明Cbx7 通过 Hippo 通路调控脑胶质瘤侵袭/迁移的机制。预期研究结果将揭示Cbx7-Hippo 通路是调控脑胶质瘤进展的新的信号通路，Cbx7 是人类 Hippo 通路的上游调节子，为脑胶质瘤的分子靶向治疗提供新的理论依据与治疗靶点。

Hippo pathway is a newly discovered protein kinase pathway that regulates the invasion and migration of cells. The imbalance of Hippo pathway is closely related to the malignant progression of tumor, but its upstream regulatory mechanism is lack of research. Although Cbx7 has been shown to inhibit tumor progression in a variety of human tumors, the exact mechanism is unclear. Based on our preliminary finding that Cbx7 can inhibit the invasion and migration of glioma cells and activate the Hippo pathway, the aim of this project is to study the effect of Cbx7 on the regulation of cell invasion and migration, including glioma specimens, cultured cells and nude mice. Cbx7 regulates the level and activity of key proteins in the Hippo pathway, and clarifies the exact mechanism that Cbx7 regulates glioma invasion and migration through the Hippo pathway. It is expected to reveal that Cbx7-Hippo pathway is a new signaling pathway regulating glioma progression and Cbx7 is the upstream regulator of human Hippo pathway, which will provide a new theoretical basis for molecular targeted therapy of glioma .