炎症促进肝癌转移分子机制不明，转录因子激活在其中发挥重要作用。前期我们率先发现：①FoxM1通过转录激活MMP-7、RhoC和ROCK1表达促进肝癌转移；②抑制TNF-α效应激酶IKKα显著降低TNF-α诱导的FoxM1过表达；③IKKα 不仅上调FoxM1表达，并与FoxM1结合增强其转录活性；④IKKα与FoxM1在肝癌组织中表达正相关，其共同阳性表达提示预后不良。据此推测：IKKa/FoxM1途径可能在炎症介导肝癌转移中发挥重要作用。然而，IKKa上调FoxM1表达并增强其转录活性的机制是什么？抑制IKKa/FoxM1途径能否有效减轻肝癌转移？尚不清楚。本课题拟通过EMSA、ChIP、荧光报告基因、质谱、体内外转移实验，IKKα肝脏特异转基因鼠体内干预等一系列实验阐明以上两个问题。研究结果有望拓展对IKKα和FoxM1功能的新认识以及为肝癌治疗提供新的干预靶点。

Metastasis is the major cause of death in hepatocellular carcinoma (HCC), but the complex mechanism of inflammation-mediated metastasis is far from being understood. Forkhead box M1 (FoxM1) is a master regulator of tumor metastasis that plays an important role in the development of HCC. However, whether or not FoxM1 contributes to the inflammation-induced HCC metastasis remains unknown. In the previous study, we found that FoxM1 promoted HCC metastasis through transactivation of MMP-7, RhoC, and ROCK1 expression. In addition, Knockdown of IKKa by siRNA impaired TNFa-mediated FoxM1 upregulation. IKKα interacted with and enhanced FoxM1 transcriptional activity. Furthermore, IKKα expression was positively correlated with FoxM1 expression in human HCC tissues, and their coexpression indicated poor prognosis of HCC. Thus, we hypothesized that IKKα/FoxM1 signaling pathway may play a positive role in inflammation-mediated HCC metastasis. In this study, we are going to explore the regulatory mechanism of FoxM1 activation mediated by IKKα.This study may provide a target for clinical intervention of HCC.