申请者所在课题组通过基因芯片和real-time PCR验证，确认了一系列与大肠癌转移相关的特异性功能分子。由此关注到一个尚未在肿瘤中存在报道的基因- - AZGP1在同时性肝转移组较无肝转移组升高2.36倍，而在异时性肝转移组升高1.77倍，提示其可能与肝转移相关。在此基础上，本项目拟通过：1）大规模组织标本中验证AZGP1与结直肠癌肝转移的关系；2）构建过表达、RNAi和功能回复的慢病毒载体，上调和下调大肠癌细胞中AZGP1的表达，观察AZGP1表达下调后大肠癌细胞形态和侵袭转移能力的变化，并在动物模型上验证；3）应用免疫共沉淀和酵母双杂交两种不同的筛选方法，探寻与AZGP1发生相互作用的蛋白分子，通过体外和体内实验验证AZGP1与候选蛋白的相互作用并明确其作用方式，研究AZGP1在细胞信号通路中的定位，探索AZGP1在肿瘤转移发生途经中可能的定位和分子机制。

In order to understand the molecular basis of liver metastasis(LM) of colorectal cancer(CRC),our research group analyzed the tissue from colorectal cancer using whole human gene chip. All tissues were divided into three groups: CRC without LM, CRC with synchronous LM and CRC with metachronous LM according to our own follow-up database including more than 2000 cases and the time span was longer than 10 years. We found some new genes which could be one of the important role in liver metastasis of colorectal cancer. AZGP1 was one of these genes, which was found 2.36 fold in synchronous LM and 1.77 fold in metachronous LM than those CRC without LM. We want to do some works confirming the molecular mechanism of AZGP1 in liver metastasis of CRC: 1) Clinical veification: RT-PCR and immunohistochemistry to verify the expression of AZGP1 and liver metastasis of CRC；2）To build the letivirus vectors, we would study the changes of proteins in CRC cells when we regulate the expression of AZGP1 in cell and aninmal modles. 3) We use coImmunoprecipitation to study the changes of expression of AZGP1 and its proteins, also we would focus on the changes of CRC cell behaviours. 4) We use Yeast TwoHybrid System to study the changes of expression of AZGP1 and its proteins, also we would focus on the changes of CRC cell behaviours. Through all these studies, we want to verify the molecular basis of AZGP1 in the liver metastasis of colorectal cancers.