SphK1/S1P信号通路在人结肠癌侵袭转移中对FAK介导的上皮间质转化的影响及其机制研究

项目名称： SphK1/S1P信号通路在人结肠癌侵袭转移中对FAK介导的上皮间质转化的影响及其机制研究

项目编号： No.81460380

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘诗权

作者单位： 广西医科大学

项目金额： 47万元

中文摘要： 研究表明上皮间质转化（EMT）在肿瘤的侵袭转移中发挥重要作用，而黏着斑激酶（FAK）被认为是调控EMT的关键因素之一。我们前期研究发现SphK1/S1P信号通路通过激活FAK促进结肠癌的侵袭转移；且有转移结肠癌组织中EMT主要标记物E-钙粘蛋白的表达较无转移结肠癌组织明显减弱，而波形蛋白则明显增强，这些标记物表达的变化与SphK1的表达密切相关。因此，我们推测SphK1/S1P信号通路可能是通过调控FAK介导的EMT从而促进结肠癌侵袭转移。本课题拟检测正常结肠粘膜、有转移和无转移结肠癌组织中SphK1/S1P和FAK通路以及EMT相关蛋白的表达；同时，采用基因工程技术及原位移植瘤模型等方法探讨体外及体内结肠癌细胞SphK1/S1P信号通路对FAK介导的EMT及细胞侵袭转移能力的影响，为阐明人结肠癌侵袭转移机制，寻找治疗结肠癌新靶点提供实验依据。

中文关键词： C08_结；直肠肿瘤；上皮间质转化；鞘氨醇激酶-1；黏着斑激酶；转移

英文摘要： Evidences show that epithelial-mesenchymal transition (EMT) plays important roles in cancer metastasis, and focal adhesion kinase (FAK) is thought to be a key regulating factor of EMT. Our recent studies showed that the expression of sphingosine kinase 1 (SphK1), FAK and p-FAK in colon cancer tissues was associated with Dukes' stage, lymph node metastasis and distant metastasis. There was a close correlation between the expression of SphK1 and FAK or p-FAK. Morover, cell invasiveness and expression of FAK were enhanced with the overexpression of SphK1 in colon cancer cells. Studies also showed that the expression of E-cadherin in colon cancer tissues with metastasis was slight than that of colon cancer tissues with metastasis, contrastly, the expression of vimentin was increased, and the expression of E-cadherin and vimentin were closely relative with the expression of SphK1. Thus, it is considerated that SphK1/S1P signaling pathway promotes colon cancer metastasis through regulating EMT mediated by FAK. In this study, the expression of factors which involved in EMT, SphK1/S1P and FAK signal pathways will be investigated in tissues of normal colonic mucosa, colon cancer with or without metastasis. In addition, the effects of SphK1/S1P signal pathway on FAK mediated EMT in colon cancer metastasis will be studied in vivo and in vitro by gene engineering technology and the orthotopic transplantation tumor model. This study will elusidate some mechanisms of colon cancer invasion and metastasis and provide the experimental basis for exploring new therapeutic target on human colon carcinama.

英文关键词： colon cancer;epithelial-mesenchymal transition;sphingosine kinase 1;focal adhesion kinase;metastasis