结直肠癌（Colorectal cancer，CRC)是世界范围和我国高发的恶性肿瘤，肝转移是其致死的主要原因。本课题组前期研究发现抑癌基因WTX通过与RhoGDIa结合，在抑制结直肠癌进展及肝转移过程中发挥重要作用。我们预测应用多肽模拟WTX对RhoGDIa的结合，可能实现抗结直肠癌肝转移效果。为构建有效的WTX模拟多肽，本研究拟分析WTX蛋白三维结构及其与RhoGDIa结合的蛋白结构域，并合成WTX的RhoGDIa结合多肽（WTX_Rp）；明确WTX_Rp对结直肠癌细胞体外迁移和体内转移的抑制作用；最后合成WTX_RpCEA纳米药物验证其临床抗肝转移价值及分子机制和药物毒性。本项目通过对WTX蛋白结构分析和抗结直肠癌肝转移靶向药物挖掘方面的探索，有望首次构建WTX蛋白三维结构、开发WTX_RpCEA多肽纳米药物用于晚期结直肠癌的治疗，具有重要的研究价值和良好的应用前景。

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and in China. Liver metastasis is the main cause of these patients’ death. Our previous studies have found that WTX plays an important role in inhibiting the progression and liver metastasis of colorectal cancer by binding with RhoGDIa. We predicte that to use the polypeptide to imitate the combation of WTX with RhoGDIa may achieve the effect of anti-liver metastasis of colorectal cancer. In order to construct an effective WTX mimic polypeptide, this study intends to analyze the three-dimensional structure of WTX protein and its binding domain with RhoGDIa, and synthesize WTX-binding polypeptide (WTX_Rp), to clarify the inhibitory effect of WTX_Rp on the migration and metastasis of colorectal cancer cells in vitro and in vivo, and finally synthesize WTX_RpCEA nanodrug to verify its clinical anti-liver metastasis value, molecular mechanism and drug toxicity. This project is expected to construct the three-dimensional structure of WTX protein for the first time and develop WTX_RpCEA polypeptide nanodrug for the treatment of advanced colorectal cancer by analyzing the structure of WTX protein and exploring targeted drugs for anti-liver metastasis of colorectal cancer. It is believed that this project will have important research value and good application prospects.