Hippo 通路是新发现的调节细胞增殖/凋亡的蛋白激酶通路，其失调与肿瘤发生密切相关，但其上游调控机制缺乏研究。虽然幼虫巨大致死基因 Lgl 的人类同源物Hugl-1早就被假定为人类肿瘤的抑制子，但其具体作用与机制尚未阐明。基于我们初步发现Hugl-1有抑制脑胶质瘤细胞生长及激活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，以调节细胞增殖/凋亡的Hippo 通路为切入点，从分子、细胞与整体水平研究Hugl-1对脑胶质瘤细胞生长（增殖/凋亡、侵袭/迁移）的影响；Hugl-1对Hippo 通路关键蛋白的水平与活性的调节；阐明Hugl-1通过Hippo 通路调控脑胶质瘤生长的机制。预期研究结果将揭示Hugl-1-Hippo通路是调控脑胶质瘤生长的新的信号通路，Hugl-1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。

The Hippo pathway is an evolutionally conserved, newly found protein kinase cascade governing cell proliferation and apoptosis. Deregulation of the Hippo pathway is closely related to cancer development, but the regulatory mechanism of hippo pathway is totally lack of study in mammalian. Although Hugl-1, the mammalian homolog of lethal giant larvae (Lgl), is supposed as a tumor suppressor in human for a long time, the detail roles and mechanisms of Hugl-1 in human cancer are largely unknown so far. Our preliminary data showed that restore of Hugl-1 suppressed the glioma cell growth and promoted Hippo pathway activation. Thus, by using the glioma specimens, cultured glioma cells and nude mice and starting from Hippo pathway, the key protein kinase cascade regulating cell proliferation and apoptosis, we determine to study the detail roles of Hugl-1 in glioma cell growth, the regulatory role of Hugl-1 in Hippo pathway in this study. Our results will not only elucidate the mechanism that Hugl-1 regulates glioma progression through Hippo pathway, but also provide valuable idea for finding the upstream regulator of Hippo pathway, for the first time, in human cancer, and potential targets for molecular therapy of brain gliomas.