肝癌是我国死亡率第三位的肿瘤，复发转移是其预后差的重要原因。肿瘤细胞进入脉管后需获得抵抗失巢凋亡的能力才能继续生存并最终形成转移灶。失巢凋亡抵抗是肿瘤转移的先决条件，在肿瘤细胞靶向转移过程中发挥重要作用。我们发现失巢凋亡抵抗肝癌细胞亚群较亲本细胞靶向肺微血管内皮细胞（HPMECs）迁移的能力增强；且随着细胞失巢凋亡抗性的增强，AEG1表达亦显著提高。而沉默AEG1的表达后细胞靶向HPMECs迁移的能力明显下降，提示AEG1可能介导失巢凋亡抵抗肝癌细胞靶向肺迁移。我们还发现AEG1可能通过ERK1/2/FOXC2通路调控细胞迁移相关趋化因子CXCR4表达，而HPMECs高表达和分泌CXCR4的配体CXCL12。本课题拟证实失巢凋亡抵抗肝癌细胞亚群通过上调AEG1表达，激活ERK1/2/FOXC2通路，从而调控CXCR4/CXCL12轴介导的该细胞亚群靶向HPMECs迁移，促进肝癌肺转移发生。

Hepatocellular carcinoma is the third leading cause of cancer-related death in china, and metastasis contributes the poor prognosis of HCC. Anoikis resistant protects Tumor cells from apoptosis induced by cell matrix detachment and promotes metastasis. Anoikis resistance is a prerequisite for tumor metastasis, playing an important role in the process of targeted metastasis of tumor cells. Our previous study found that the sub-population of anoikis-resistant HCC cells have a greater ability to migrate toward lung than parental cells. With the acquisition of anoikis resistance, the expression of AEG1 increased significantly in HCC cells. The ability of migrating targeting HPMECs was significantly decreased in anoikis resistant HCC cells by silencing AEG1, which suggested that AEG1 may mediate targeted lung migration in anoikis resistant HCC cells. Our research suggests that AEG1 may regulate the expression of chemokine CXCR4 associated with targeted metastasis, meanwhile CXCL12, a ligand of CXCR4, was highly expressed and secreted in HPMECs. This study is prepared to confirm that up-regulation of AEG1 can mediate migration targeted HPMECs in anoikis resistant HCC cells by CXCR4/CXCL12 axis via activating ERK1/2/FOXC2 pathway, and finally promote lung metastasis of HCC.