SHP-1是由PTPN6基因编码的含有SH2结构域的非受体型蛋白酪氨酸磷酸酶，可通过催化靶基因酪氨酸去磷酸化作用影响细胞增殖、分化、活性和凋亡。既往研究报道SHP-1可通过阻断炎症反应抑制肝癌的发生，但其在肝癌转移过程中的作用及其机制目前尚未完全明确。本课题拟检测人肝癌标本中SHP-1表达量与肝癌恶性表型及预后的关系；利用重组复制缺陷型腺病毒和小干扰RNA技术调控SHP-1表达，观察其对肝癌细胞侵袭、迁移能力的影响；并利用肝细胞特异性SHP-1基因敲除小鼠，观察肝细胞SHP-1表达缺失对肝癌细胞在小鼠体内转移的影响；在此基础上深入研究SHP-1抑制肝癌的分子机制，探讨SHP-1是否通过其去磷酸化作用抑制肝癌转移；研究结果将进一步阐明SHP-1在抑制肝癌发生发展中的作用及分子机制，为肝癌的诊断和治疗提供新靶点。

The Src-homology 2-domain-containing protein tyrosinephosphatase-1（SHP-1）encoded by PTPN6 gene plays an important role in cell proliferation, differentiation, activation and apoptosis by dephosphorylation. Previous studies have shown that SHP-1 could inhibit the occurrence of HCC by blocking inflammatory pathways. However, the role of SHP-1 in HCC metastasis and the potential mechanism is still not fully clarified. Firstly, this study aims to investigate the relationship between SHP-1 expression level and HCC progression in clinical samples. Then, the effect of SHP-1 on the migration and invasion of HCC cells will be detected by using replication-deficient adenovirus vector and small interference RNA. Furthermore, we will use hepatocyte-specific PTPN6 deletion gene knockout mice to observe the effects of SHP-1 on the metastasis of HCC cells in vivo. Finally, we will explore the underlying molecular mechanism of SHP-1 in inhibiting HCC metastasis. Generally, this study will determine the effect and mechanism of SHP-1 on the metastasis of HCC and provide novel targets for the diagnosis and treatment of HCC.