结直肠癌（CRC）是常见的消化道肿瘤，转移是CRC患者预后差以及致死的重要因素。既往研究证实E-cadherin/β-catenin复合体的再循环失调在肿瘤发生及转移中扮演重要角色，然而相关调控机制尚不完全清楚。课题前期基于高通量测序数据筛查确定再循环相关蛋白REP15（Rab15效应蛋白）在CRC中表达下调，且不利于患者预后。最新预实验发现REP15缺失可影响E-cadherin/β-catenin表达并促进肠癌细胞的迁移能力，提示REP15可能通过调节E-cadherin/β-catenin的再循环进而影响CRC转移。为证实这一假说，课题拟通过组织样本、细胞模型以及体内肝转移模型阐明REP15影响CRC转移的机制；结合生物素标记、流式细胞术及免疫荧光等方法研究REP15对E-cadherin/β-catenin的再循环调控。本课题的完成将为深入认知CRC分子发病机制提供新的理论依据。

Colorectal cancer (CRC) is a common gastrointestinal tumor, and metastasis is a major factor for poor prognosis and cause of mortality in patients with CRC. Previous studies have confirmed the dysregulation of the E-cadherin/β-catenin complex recycling play a vital role in tumorigenesis and metastasis. However, the regulation mechanism on E-cadherin/β-catenin recycling is not fully understood. Based on high-throughput sequencing data, we screened and identified recycling-related protein REP15 (Rab15 Effector Protein) is down-regulated in CRC, which is unfavorable for patients' survival. In the latest study, we observed that REP15 deletion could affect the expression of E-cadherin/β-catenin and promote the capacity of colon cancer cell migration, indicating that REP15 may participate in the process of CRC metastasis via E-cadherin/β-catenin regulation. To confirm this hypothesis, this project aims to clarify the mechanism on REP15-mediated CRC metastasis using tissue samples, cell models, and in vivo liver metastasis models; to study the regulation of E-cadherin/β-catenin recycling by biotin labeling, flow cytometry, immunofluorescence, and other methods. The completion of this project will provide a new theoretical basis for understanding the molecular pathogenesis of CRC.