识别肿瘤微环境的重要构成并解析其中调控机制是当前肿瘤研究的重要课题。肿瘤相关巨噬细胞(TAM)是胶质瘤组织中最丰富的非肿瘤细胞，并大多极化为M2型发挥促癌作用。申请人前期发现HEXB参与构成胶质瘤细胞与TAM恶性正反馈环路，并通过抑制Hippo信号加速胶质瘤细胞糖酵解，因此提出“M2型TAM通过HEXB调控胶质瘤糖酵解的机制研究”。项目将在共培养体系中干预HEXB，检测胶质瘤糖酵解变化，探究M2型TAM是否依赖HEXB调节胶质瘤糖酵解过程；运用体内外实验平台，研究HEXB干预下Hippo通路与细胞糖酵解之间的作用关系，明确HEXB是否通过抑制Hippo信号发挥糖酵解促进作用；应用蛋白截短/突变技术，确定HEXB与Hippo信号上游抑制分子ILK的结合位点，并深入研究HEXB稳定ILK调控Hippo信号的分子机制。本项目将在肿瘤微环境与代谢重编程交叉领域进行有益探索，完善HEXB作用机制。

Identifying the important components of tumor microenvironment and exploring their regulatory mechanisms are the important topics in current cancer research. Tumor-associated macrophages (TAM)s are the most abundant non-tumor cells within glioma tissues. Most of TAMs are polarized into oncogenic M2 subtype. In previous study, we found that HEXB forms a malignant positive feedback loop between glioma cells and TAMs. HEXB facilitates glioma malignancy by repressing Hippo signaling and activating glycolysis. Here, we propose a project of "The mechanism of M2 TAM activating glioma glycolysis by HEXB". The project will interfere HEXB in the co-culture system to detect the change of glioma glycolysis, and explore whether M2 TAM regulates the glycolytic status of glioma cells through HEXB. The relationship between Hippo signaling and glycolytic status will be studied under HEXB intervention to clarify whether HEXB regulates glycolysis through Hippo signaling. We will also explore the binding sits between HEXB and ILK, a key upstream repressor of Hippo pathway. Their regulatory relationship will be fully investigated to clarify the mechanism of HEXB in suppressing Hippo pathway and facilitating glioma glycolysis. Taken together, this project will explore the interaction between tumor microenvironment and metabolic reprogramming, and try to elaborate the oncogenic mechanism of HEXB in glioma.