马达蛋白KIF5B在结直肠癌浸润和转移中的作用及机制研究

胞内运输是细胞信号转导的重要环节之一，其功能紊乱会导致多种疾病的发生。既往研究发现，在多种肿瘤发生时，马达蛋白KIF5B的表达异常，但是KIF5B是否参与了结直肠癌的浸润和转移尚未见报道。我们前期发现，KIF5B在结直肠浸润癌和肝转移癌组织中的表达量低于原位癌；KIF5B与E-cadherin免疫共沉淀；敲低KIF5B激活DAPK1/ZEB1信号通路，促进EMT标志物表达。据此提出假说，KIF5B表达失调导致E-cadherin不稳定，诱导β-catenin入核，激活DAPK1-ZEB1信号通路，导致EMT，促进肿瘤的浸润和转移。本研究拟通过临床结直肠癌手术标本，利用细胞和动物肿瘤转移模型，通过组织芯片、生物信息学、免疫组化、RNA和蛋白质分析等方法，探讨KIF5B在结直肠癌浸润和转移中的作用和机制。本研究将从胞内运输这个新视角为揭示肿瘤浸润和转移的机制，为结直肠癌的治疗奠定理论基础。

Intracellular transport is important for cellular signal transduction, and its dysfunction results in various diseases. It was found that desregulation of KIF5B expression occurs in various tumors, however, whether KIF5B is involved in the invasion and metastasis of colorectal cancer has not been reported. Oure preliminary results revealed that the expression of KIF5B in colorectal invasive cancer and liver metastatic cancer is lower than that in cancer in situ; E-cadherin could be immunoprecipitated with KIF5B; knockdown of KIF5B activates DAPK1/ZEB1 signaling pathway and the expression of EMT markers. Therefore, we hypothesize that, dysregulation of KIF5B expression leads to instability of E-cadherin, induces nuclear translocation of β-catenin, activates DAPK1-ZEB1 signaling pathway, leads to EMT, promotes tumor invasion and metastasis. This study aims to investigate the role and underlying molecular mechanism of KIF5B in the invasion and metastasis of colorectal cancer through clinical colorectal cancer surgical specimens, cell and animal tumor metastasis models, and tissue microarray, bioinformatics, immunohistochemistry, RNA, and protein analysis. And mechanism. This study will provide new insights for the study and treatment of colorectal cancer metastasis.