结直肠癌是消化道主要恶性肿瘤，转移和耐药是导致结直肠癌患者预后差的重要原因。前期我们研究发现酪氨酸磷酸酶受体蛋白PTPRK的表达在不同病理分期结直肠癌患者中变化趋势相反，PTPRK在结直肠癌早期形成和晚期转移中可能起着不同作用。本课题中我们将开展深入研究，通过细胞实验和动物模型明确PTPRK在早期结直肠癌形成中的抑癌和晚期肿瘤转移中的促癌基因功能；阐明PTPRK在结直肠癌形成和转移中出现这种双重功能的分子机制，特别是PTPRK通过c-Src/P53/CD44信号轴促进癌细胞转移的机制；搞清楚结直肠癌中引发PTPRK功能反转的关键分子事件；揭示PTPRK及其激活的c-Src信号对5-FU化疗敏感性的影响；最后尝试建立PTPRK与其它分子标记物相结合的综合预测模型。相信后续工作既可为结直肠癌的基础研究提供理论证据，也可为不同时期结直肠癌的精准治疗和预后分析提供新靶点。

Colorectal cancer (CRC) is one of the main malignant tumors of digestive tract. Metastasis and drug resistance are the main causes of poor prognosis in CRC patients. In our previous work, we found that the expression changes of the protein tyrosine phosphatase receptor type K (PTPRK) showed an opposite trend in CRC patients at different pathological stages, and PTPRK might play different roles in early tumor formation and late-stage CRC metastasis. In this project, we will carry out comprehensive studies to clarify the tumor suppressor function of PTPRK in early tumorigenesis and its oncogenic role in late-stage CRC metastasis through cell experiments and animal models, and elucidate the molecular mechanism of PTPRK-mediated dual functions in CRC, especially how to regulate c-Src/P53/CD44 signal axis to promote CRC metastasis. We will also investigate the key molecular events leading to PTPRK functional reversal in CRC; and at the same time figure out the effects of PTPRK and PTPRK-activated c-Src signaling on chemosensitivity of 5-FU. Finally, we will try to establish a therapeutic and prognostic prediction model using PTPRK combined with other molecular markers. We believe that our follow-up work will not only provide theoretical evidence for the basic research of CRC, but also provide novel targets for CRC precise treatment and prognosis analysis.