CDK5(cyclin-dependent kinase 5）与多种恶性肿瘤的增殖、转移密切相关，但目前尚缺乏对CDK5通路及其调控的下游分子在肝癌发生、发展中作用的完整认识。我们前期研究发现CDK5在原发性肝癌中显著高表达且与微血管侵犯及复发具有相关性，并使用SILAC技术筛选出CDK5调控的下游底物TPX2（Target protein for Xklp2），本研究将以TPX2为代表，验证CDK5通过调控TPX2进而促进肝癌发生的机制，并研究最新报道的CDK5激酶抑制剂他莫昔芬是否通过干扰CDK5-TPX2这一通路抑制肝癌的恶性表型。为CDK5及其下游底物作为临床评价肝癌预后的标记分子及开展可能的靶向治疗奠定理论基础。

It has been reported that CDK5(cyclin-dependent kinase 5)play an important role in proliferation and metastasis of various malignant tumors, but CDK5 pathway and its substrates in genesis and development of HCC are still unclear. Our previous study found that CDK5 was increased in HCC tisues and the level of CDK5 was associated with microvascular invasion(MVI) and recurrence of HCC. The phosphorylated substrate of CDK5, TPX2(Target protein for Xklp2), which was associated with tumor, has been selected by phosphoproteome analysis(SILAC). TPX2 has been selected by these study. We will verify that CDK5 promote HCC through its substrate TPX2. Meanwhile, tamoxifen, a new inhibitor of CDK5 kinase activity, will be used to verify its inhibition of HCC by regulateing CDK5-TPX2 pathway. These study will pave the way for application of CDK5 and its subtrates as promising makers in clinical evaluation of prognosis and target molecules of cancer therapy in HCC.