可溶性的TRAIL能够诱导肝癌细胞的凋亡，但是其在细胞内的具体作用机制却知之甚少。本课题组利用Co-IP结合LC-MS/MS首次发现可溶性TRAIL与IER3存在相互作用，采用Wnt信号通路试剂盒，筛选出TRAIL与IER3下调WISP1的表达，为此我们提出假说：TRAIL与IER3协同作用诱导肝癌细胞凋亡，其生物学效应是通过调控Wnt/β-catenin/WISP1信号通路实现的。为了验证这一假说，我们以人肝癌细胞系和裸鼠肝癌动物模型为研究对象，采用Real time PCR、Western blot、FACS、过表达和RNA干扰等手段，从分子、细胞、组织以及动物水平探讨WISP1在TRAIL与IER3介导的肝癌细胞凋亡中的重要作用，明确TRAIL与IER3通过Wnt/β-catenin/WISP1信号通路促进肝癌细胞凋亡的调控机制，为肝癌的预防治疗提供新的理论和实验依据。

The ability of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) to induce apoptosis of hepatocellular carcinoma cells has been widely demonstrated, but its specific intracellular mechanism is not well defined. Combined with Co-IP and LC-MS/MS, the interaction between TRAIL and IER3 was identified for the first time by our group. Of the Wnt signaling pathway array kit, WISP1 showing a significate downregulation by TRAIL and IER3 treatment. We proposed the hypothesis: TRAIL and IER3 induced apoptosis of hepatocellular carcinoma cells by regulating Wnt/β-catenin/WISP1 signaling pathway. To test this hypothesis, we established human hepatoma cell lines and animal models of hepatocellular carcinoma in nude mice to investigate the function of WISP1 in HCC apoptosis. Real time PCR, Western blot, FACS, over-expression and RNA interference were examined to explore the important role of WISP1 in the TRAIL and IER3 treatment groups through the molecular, cellular, tissue and animal levels. Our study provides evidence that TRAIL and IER3 exerted apoptosis of hepatocellular carcinoma cells by modulating Wnt/β-catenin/WISP1 signaling. It is opening up a new theory and experimental mechanism for the prevention and treatment of HCC.