侵袭转移是导致肝癌预后不佳的主要原因。我们的前期工作发现smad3在肝癌组织中的表达与手术后复发相关。在肝癌细胞系中高表达smad3可以促进肿瘤细胞的侵袭和转移，同时伴随着RPTPε的高表达和JNK、ERK、AKT通路的激活。基于此及其他相关研究结果，我们推测肝癌细胞中，smad3的过表达可以诱导RPTPε的表达，RPTPε通过其酪氨酸磷酸酶活性激活下游的EGFR、FAK激酶、Scr激酶，进而激活JNK、ERK、AKT等非smad依赖通路，诱导下游基因的转录，促进肿瘤的侵袭转移。为了验证上述假说，我们构建smad3过表达和smad3敲减肝癌细胞系，研究smad3对肝癌侵袭转移的作用及相关信号通路的活化；然后在构建的细胞系中稳定表达或敲减RPTPε，进一步研究RPTPε在smad3介导的肝癌侵袭转移过程中的作用，并阐明RPTPε对TGF-β通路网络的调控作用。

Invasion and metastasis is the main cause leading to the poor prognosis of hepatocellular carcinoma. Our previous study shows the overexpression of smad3 in the HCC tissues is correlated with postoperative recurrence. Overexpression of smad3 in HCC cell lines enhances their invasive and metastatic ability, accompanied with up-regulation of RPTPεand activation of JNK, ERK, AKT pathways. Based on our preliminary works and the results of other related studies, we speculate that overexpression of smad3 induced the expression of RPTPε, which activated downstream EGFR, FAK and Scr, result in the activation of smad independent signaling pathways such as JNK、ERK and AKT pathway and induced invasion and metastasis of HCC. In order to confirm our hypothesis, we established smad3 overexpressed cell line and smad3 knockdown cell line to research the effect of smad3 in invasion and metastasis of HCC and the activation of related signaling pathways; then we overexpress or knockdown RPTPε in these cell lines, to study the effect of RPTPεin smad3 induced invasion and metastasis, and definite the regulative effect of RPTPε in TGF-βsignaling pathways.