肿瘤转移是导致结直肠癌病患死亡的主要原因。本课题组先期利用激光捕获显微镜切割技术精确分离结直肠癌前缘单个肿瘤芽细胞、肿瘤细胞和正常粘膜细胞，表达谱芯片筛选差异筛选结果发现前列腺跨膜蛋白PMEPA1在肿瘤芽细胞和肿瘤细胞中表达均明显上调，且其表达与肿瘤转移、TMN分期和预后有关，推测PMEPA1在结直肠癌上皮细胞间充质转化（EMT）和转移过程中发挥重要作用。在此基础上我们拟通过构建PMEPA1过表达和shRNA载体模型研究其在调控结直肠癌发生发展中的作用，采用免疫共沉淀技术结合CRISPR/Cas9技术研究PMEPA1直接相互作用蛋白及关键位点，明确PMEPA1在结直肠癌中是否依赖雄激素受体（AR）信号通路调控结直肠癌EMT和转移，解决PMEPA1在肿瘤中的双相作用机制等问题。以上机制的阐明可能实现将以PMEPA1的表达和AR活化程度对结直肠癌进行分层进而实现结直肠癌的预防和精准治疗。

The metastasis is a major cause of cancer mortality of colorectal cancer. In our previous study, the tumor budding cells, tumor cells and normal intestinal epithelial cells were isolated and captured using laser capture microdissection. The data from microarray showed PMEPA1 was up-regulated in tumor budding cells and tumor cells compared with normal epithelial cells, which expression was positively correlated with metastasis, TNM stage and poor survival. In this study the roles of PMEPA1 in colorectal cancer EMT and metastasis will be investigated through overexpressing and knocking down PMEPA1. And the interaction targets with PMEPA1 and their critical domain would be verified by Co-Immunoprecipitation combined with CRISPR/Cas9 technology. Furthermore we want to know whether PMEPA1 regulates colorectal cancer EMT and metastasis dependent on or independent on androgen receptor (AR) pathway, and to clarify the disparity function of PMEPA1 in between different types of tumors. This study will provide a novel target for cancer prevention and precision medicine.