肝癌属于高致死率肿瘤，在我国的发病率居高不下，已经给人民生活健康带来严重负担。临床研究发现纤维凝胶蛋白3(FCN3）在肝癌中显著下调, 提示其可能与肝癌发生发展密切相关。FCN3是参与补体反应的重要成分，然而FCN3对肝癌的作用和机制鲜有报道。申请人前期研究发现FCN3具有显著抑制肝癌的作用，而且全身敲除补体反应关键调控元件C3并不影响FCN3抑制肝癌的作用，同时申请人发现FCN3可以通过激活AMPK抑制肝脏中脂滴累积，申请人通过质谱筛选，发现FCN3与K型受体蛋白酪氨酸磷酸酶（PTPRK）相互结合。基于以上发现，申请人猜测FCN3通过激活PTPRK-AMPK信号通路调控了肝脂累积，进而抑制了肝癌的进程。本项目拟研究FCN3通过影响PTPRK和AMPK等重要节点调控脂代谢的机制，以及FCN3介导的脂代谢抑制对于肝癌进程的拮抗作用，以期为肝癌的防治提供重要的理论依据。

Due to the high incidence and mortality, liver cancer remains a major health burden in China. Previous clinical analysis has documented that the expression of FCN3, a key regulator of complement reaction, is significantly down-regulated in liver cancer, suggesting that FCN3 might play an important role in the prevention and treatment of liver cancer. However, the effect of FCN3 on the development of liver cancer has not been well studied yet. The applicant`s previous work revealed that FCN3 significantly suppressed the progression of hepatocellular carcinoma, and globally knock-outing of C3, which is the key control component of complement reaction, had little effect on the FCN3-mediated suppression of hepatocellular carcinoma. Moreover, the applicant found that FCN3 inhibited lipid accumulation in the liver by activating AMPK，and the applicant also disclosed the interaction between FCN3 and protein tyrosine phosphatase receptor type K (PTPRK) with mass spectrometry screening. These results prompted the applicant to hypothesize that FCN3 suppresses hepatocellular carcinoma progression via PTPRK-AMPK-lipid metabolism axis. The proposed project aims to explore the mechanism underlying FCN3 suppressing the development of hepatocellular carcinoma, which would provide novel theoretical basis for the treatment of liver cancer.