肝星状细胞(HSC)在促进肝癌侵袭转移中发挥重要作用，但机制尚不明确。我们近期研究发现：MSI2在HSC促进肝癌细胞(HCC)侵袭转移的过程中发挥重要作用；MSI2在激活的HSC中高表达；干扰肝星状细胞MSI2表达，可以显著削弱HSC对HCC侵袭转移的促进作用；PCR芯片检测结合公开数据挖掘提示MSI2促进细胞因子CXCL1的分泌。因此，我们推测肝星状细胞MSI2可能通过调节其细胞因子CXCL1表达促进肝癌细胞侵袭转移。本研究拟通过HSC/HCC共培养、荧光素酶报告、HSC/HCC裸鼠皮下共移植瘤、肝纤维化小鼠肝原位移植瘤模型等手段，验证肝星状细胞MSI2对HCC侵袭转移的促进作用，明确肝星状细胞MSI2促进肝癌侵袭转移的分子机制。本项目旨在阐明肝星状细胞MSI2/CXCL1轴促进肝癌侵袭转移的分子机制，为寻找潜在的肝癌治疗靶点提供理论基础。

It is still unclear that how hepatic stellate cell (HSC) enhances the invasion and metastasis ability of hepatocellular carcinoma (HCC). Our recent studies demonstrated that MSI2 was upregulated in activated hepatic stellate cells. In HSC/HCC co-culture system, we found that interference of MSI2 expression in HSC significantly decreased the invasion ability of co-cultured HCC cells. PCR array combined with data mining in public data base indicated that MSI2 may promote the secretion of cytokine CXCL1. Therefore, we hypothesized that overexpression of MSI2 in HSC facilitated invasion and metastasis of HCC cells via promoting CXCL1 expression. To validate this hypothesis and investigate the underlying mechanism, we will use experiments include HSC/HCC co-culture, luciferase reporter, nude mice subcutaneous HSC/HCC co-transplanted tumor models, liver orthotopic transplantation tumor model based on liver fibrosis mice to determine the function of MSI2/CXCL1 axis in HSCs inducing HCC invasion and metastasis. This study would help to elucidate the role of HSCs in HCC invasion and metastasis, and provide theoretical basis for investigating potential targeted therapies for HCC.