转移是结肠癌致死的主要原因，转移的发生涉及肿瘤细胞及其所处微环境中复杂的信号通路，机制还不完全清楚。MC3是我们实验室前期自主建立的一株结肠癌特异单抗，我们鉴定出其识别的抗原为Txl-2,后期发现Txl-2的剪接体Txl-2b与小G蛋白Ran相互作用，显著促进结肠癌的转移。文献表明，Ran与肿瘤的发生发展有密切关系。在此基础上，我们通过高通量PCR芯片筛选、siRNA干预，发现FOXG1、E-cad可能为Ran下游作用的关键分子。本课题拟通过慢病毒转染、体内体外功能实验验证Ran促进结肠癌的侵袭转移；通过激光共聚焦、配对免疫组化、免疫共沉淀证实Ran与FOXG1相互作用；通过抑制剂干预、位点突变等研究Txl-2-Ran-FOXG1-EMT促进结肠癌转移的分子机制。本研究旨在通过认识Ran调控结肠癌转移的机制及RAN下游信号通路的深入研究，为开发结肠癌新的治疗策略提供思路。

Metastasis accounts for the majority of cancer-related mortality and the complicated mechanism remains unclear. MC3 is a monoclonal antibody previously prepared in our laboratory, which could detect colon cancer with high sensitivity and specificity. Our previous work identified thioredoxin-like protein 2 (Txl-2) as the target of MC3 and indicated that overexpression of Txl-2 in colon cancer cells significantly promoted cancer cell motility, and the invasive and metastatic abilities. Furthermore, isoform-specific interaction was identified between Txl-2b and Ran, a Ras-related protein, by yeast two-hybrid assay and co-immunoprecipitation.Gene arrays and siRNA intervene show FOXG1 may be the key event of the downstream,and the mechanism may work with EMT. To prove the hyopthesis and to learn the mechanisms,Lentiviral co-transfection of Txl-2 and Ran will be done, followed by the observation of changes in cell invasive and metastatic potential in vitro and in vivo.Confocal study, paired immunostaining,deleting mutation and co-IP will be employed to further confirm the interaction between Ran and FOXG1.The pathway inhibitors, and western blot analysis will be used to further explore whether EMT happens in this event.The current study may provide a deep insight into how Protein Ran functions in the metastasis of CRC and open an avenue to a novel therapeutic strategy against colon cancer.