肝转移是结直肠癌(CRC)综合治疗后失败的主要原因，给临床治疗带来严峻挑战。然而，目前对于CRC肝转移的分子机制尚未完全清楚。我们近期发表文章证明信号转导因子TROP2在CRC肝转移灶中高表达并提示不良预后。进一步前期研究发现：① TROP2磷酸化PFKFB3增强CRC细胞糖酵解；② TROP2增强CRC细胞体外侵袭迁移能力；③ TROP2能促进CRC细胞体内远处转移能力；④KRAS突变能够转录上调TROP2。然而，尚不清楚TROP2如何通过糖酵解促进CRC肝转移的分子机制。因此，在前期研究工作基础上，我们假设KRAS突变转录上调TROP2，TROP2通过磷酸化PFKFB3增强CRC细胞糖酵解，进而促进CRC肝转移。本项目在此基础上，拟进一步阐明TROP2促进CRC肝转移的分子机制，为CRC肝转移预后预测提供新的标志物，并为靶向药物筛选提供重要的理论依据。

Liver metastasis is the main cause of comprehensive therapeutic failure for colorectal cancer (CRC)，which brings severe challenges to clinical treatment. To date, the molecular mechanism in development of CRC liver metastasis remains unclear. Recently, our published articles have found that signal transducer TROP2 was overexpressed in CRC liver metastasis, which indicated poor prognosis. Further preliminary study found that: (1) TROP2 enhances glycolysis in CRC cells through phosphorylation of PFKFB3;(2) TROP2 enhances the invasion and migration of CRC cells in vitro; (3) TROP2 promotes the distant metastasis of CRC cells in vivo;(4) KRAS mutation up-regulates TROP2 expression. However, it is not clear how TROP2 promotes CRC liver metastasis through glycolysis. Therefore, based on the previous results, we hypothesized that the KRAS mutation up-regulated TROP2 expression, which promoted glycolysis of CRC cells through phosphorylation of PFKFB3, and subsequently promoted CRC liver metastasis. On this basis, this project intends to further elucidate the molecular mechanism of TROP2 promoting CRC liver metastasis, in order to found out new biomarkers for prognostic prediction and provide important theoretical basis for targeted drug screening for the patients with CRC liver metastasis.