骨巨细胞瘤（GCT）是最常见的原发性骨肿瘤之一，由于较高的复发率及肿瘤对骨骼的侵蚀作用，GCT常导致患者病理性骨折、瘫痪甚至死亡，严重影响了患者的生存质量及预后。项目组以200余例GCT标本为基础，发现膜相关蛋白stomatin在GCT中表达量显著增高，同时stomatin影响了GCT增殖、侵袭及诱导血管生成的能力。通过构建骨骼系统特异性高表达stomatin的C57-sto品系鼠，发现stomatin高表达导致小鼠长骨干骺端出现类GCT样的骨缺损及病理改变。利用质谱等手段发现stomatin与Notch剪切因子γ-分泌酶结合，通过活化γ-分泌酶介导了Notch通路持续激活，这可能是导致GCT增殖及骨破坏的关键分子机制之一。项目组拟从分子、细胞及动物水平明确stomatin对γ-分泌酶活性及Notch通路的调控作用机制，为GCT的治疗提供新的基础理论依据及药物靶点。

Giant cell tumor (GCT) is one of the most common primary bone tumors. Due to its high recurrence rate and erosion of bone, it often causes pathologic fracture, paralysis, and even death, seriously affecting life quality and prognosis of patients. Based on the study of specimens of more than 200 patients with GCT, our team found membrane-associated protein stomatin was highly expressed in GCT, and meanwhile affected proliferation, invasion, and angiogenesis of GCT. We have constructed stomatin over-expression transgenic mice C57-sto and found that stomatin over-expression could lead to bone defect and pathological changes of GCT. Utilizing the means such as mass spectrometry, we found that stomatin could combine with Notch shear factor γ-secretase and activate Notch pathway, which might be the key molecular mechanisms of proliferation and bone destruction in GCT. Our team plans to explore the regulatory mechanism of stomatin on γ-secretase and Notch pathway in GCT in level of molecules, cells and animal, and furthermore provides new theory basis and drug targets for the treatment of GCT.