趋化因子Mig与受体CXCR3诱导上皮-间质转化介导舌鳞癌细胞侵袭转移的作用及机制研究

我们前期研究发现，趋化因子Mig/受体CXCR3与舌鳞癌细胞上皮-间质转化（EMT）及侵袭转移密切相关。本研究拟采用基因转染及RNA干扰技术进一步探索Mig/CXCR3诱导EMT介导舌鳞癌细胞侵袭转移的作用；免疫印迹技术检测相关信号转导途径的活性状态，分析评价Mig/CXCR3对相关信号转导途径的调控；激酶特异性活化剂和拮抗剂实现相关信号通路功能的激活和阻断，印证和诠释Mig/CXCR3诱导EMT介导舌鳞癌细胞侵袭转移的作用环节和机理；免疫组化技术检测舌鳞癌组织标本内相关因子的表达或磷酸化水平变化，行体内印证。明确Mig/CXCR3对舌鳞癌细胞EMT的诱导功能及介导侵袭转移的作用并鉴定相关信号分子，揭示和证实趋化因子/受体与肿瘤细胞EMT及侵袭转移的内在关系，以此为例从趋化因子角度诠释并推译鳞癌细胞侵袭转移的分子机制，进而为探索通过拮抗和干预趋化因子/受体信号通路逆转肿瘤侵袭转移奠定基础。

We found that the chemokine Mig/receptor CXCR3 is related to epithelial - mesenchymal transition (EMT), invasion and metastasis in tongue squamous cell carcinoma. In this study, we will further explore the role of Mig/CXCR3 in EMT and invasion and metastasis of tongue squamous cell carcinoma cells through gene transfection and RNA interference. The active state of the signal transduction pathways will be analyzed with Western blot. After activating or blocking the signal pathways with kinase-specific activator or antagonist, EMT and invasion and metastasis of tongue squamous cell carcinoma cells will be detected. Immunohistochemistry will be used to detect the changes of expression and phosphorylation of the factors in clinical specimens. Through the above study, we will define the role of Mig/CXCR3 in EMT and invasion and metastasis of oral squamous cell carcinoma cells and identify the relevant signaling molecules, interpret the molecular mechanisms of carcinoma invasion and metastasis, reveal the intrinsic relationship between the chemokine/receptor and carcinoma invasion and metastasis, explore a new way to revere carcinoma invasion and metastasis through antagonism and intervention of chemokine/receptor signal pathways.