转移是恶性肿瘤病人死亡的最主要原因。因此寻找调控肿瘤转移的关键分子对肿瘤转移的早期诊断和治疗具有重要的意义。前期我们已发表的文章报道FOXC2能够通过激活HGF-MET信号通路促进结直肠癌的转移(Oncogene.)。通过免疫共沉淀耦联质谱技术我们发现OTX1 (Orthodenticle homeobox 1)为FOXC2的结合蛋白，且OTX1在结直肠癌中的表达异常升高。进一步研究我们发现上调OTX1能够诱导结直肠癌细胞发生EMT，并促进结肠癌的侵袭及远处转移。通过全基因组表达谱芯片分析及进一步的实验验证我们发现，OTX1能够与β-catenin相结合激活Wnt/β-catenin信号通路及JAK2/STAT3信号通路。因此，本项目承前启后，深层次解析了癌基因OTX1诱导结直肠癌转移的分子机制，并与临床相结合，有望为结直肠癌的转移提供新的预后因子及治疗靶标。

Metastasis is the main cause of death in cancer patients. To identify the key molecular factors in tumor metastasis process would be great value for ealry diagnosis and therapy. Previously, we reported that FOXC2 promoted metastasis in colorectal cancer through activating HGF-MET signaling pathway (Oncogene.). Using Immunoprecipitation assay coupled with mass spectrometry analysis we indentified OTX1 (Orthodenticle homeobox 1), which is highly expressed in colorectal cancer, as a binding partner of FOXC2. Furthermore, we found that ectopic expression of OTX1 induced EMT and promoted local invasion and distant metastasis of colorectal cancer. Whole genome microarray analysis and further experiments showed that OTX1 could bind with β-catenin and activate Wnt/β-catenin signaling as well as JAK2/STAT3 pathway. In our current project, we will combine in vitro and in vivo experiments with clinical samples to deeply investigate the molecular mechanisms of OTX1-induced metastasis of colorectal cancer. Our work may help provide new prognostic factors and theraputic targets for cancer metastasis.