结直肠癌容易发生肝转移，极少量的循环结直肠癌细胞抵达肝血窦后依旧能形成肝转移瘤，这与肝内微环境因子、信号通路的交替调节肿瘤细胞的生物学特性密切相关。我们前期研究证实，在肝实质和间质细胞中，肝窦内皮分泌的巨噬细胞游走抑制因子（MIF）而非结直肠癌细胞自身的MIF能有效增强结直肠癌细胞的定向迁移，促进EMT的发生；进一步研究发现，在外分泌MIF作用下，发生EMT的结直肠癌细胞干性标志物的表达和单细胞克隆球形成能力明显增强。然而，MIF能否发挥调控肿瘤细胞干性相关因子的表达从而调节肿瘤的发生与演进,目前尚无研究报道。因此，本项目拟通过内/外源性干扰MIF的单细胞克隆球形成、低数量级细胞裸鼠成瘤及iTRAQ定量蛋白组信号分析等研究，阐明肝窦内皮分泌的外源性MIF促进结直肠癌细胞干性转化的关键作用及其分子机制，为结直肠癌多重抗转移的靶向治疗提供科学依据。

Colorectal cancer (CRC) was prone to metastasize to the liver, a few of CRC cells can form liver metastases after arriving at the hepatic sinusoidal, which was interact with the cytokines of intrahepatic and the alternation of signaling pathway regulating the biological characteristics of tumor cells. We have reported that in the liver parenchyma and stroma cells, macrophage migration inhibitory factor (MIF) released by human hepatic sinusoidal endothelial cells（HHSECs） was implicated in the chemotaxis of CRC cells. MIF paraexocrined from HHSECs, but not from the CRC cells themselves, promoted migration and epithelial-mesenchymal transition (EMT).Meanwhile, we found that HHSECs secreted MIF induced EMT in CRC cells,which strongly expressed stem cell markers ,and the ability of forming clone spheres was notably enhanced.However, there is no research reported that MIF can regulate the expression of stem cells marks which adjust the occurrence and evolution of the tumor.Therefore,series methods will be applied including clone-forming by interfere the internal or external MIF, a few of cell forming nude mice subcutaneous tumor assay,and quantitative proteomics analysis of iTRAP, etc. MIF secreted by HHSEC would be a key factor of inducing CRC cells with stemness,and the correlatived signal pathway will be verified，which might be a potential target for anticancer metastasis.