癌细胞极化运动是肿瘤侵袭转移起始阶段的核心环节，肿瘤免疫也是影响癌细胞侵袭转移的重要因素。申请者前期研究首次发现：胆管癌及其转移灶高表达aPKC-ι（调节细胞极化的关键蛋白）；并初步发现，aPKC-ι表达水平与Treg细胞浸润及免疫调节因子TGF-β1和IL-2水平增高相关；aPKC-ι表达水平也与Snail1表达相关。申请者据此推测：aPKC-ι/Snail1通路可通过调控胆管癌细胞极化影响Treg细胞功能，并介导癌细胞侵袭转移。本项目拟建立胆管癌细胞体外侵袭转移的极化运动实验模型，观察aPKC-ι高表达或失活对胆管癌细胞极化状态的调控作用，及对Treg细胞功能的影响；探讨aPKC-ι调控Snail1表达的分子机制；通过干扰aPKC-ι/Snail1通路，观察对胆管癌细胞侵袭转移的影响。本项目可望从新的角度阐明胆管癌细胞侵袭转移的分子机制，并为探索胆管癌治疗的新策略提供依据。

Polarization motion is a core aspect of the invasion and metastasis in tumor initiation stage, meanwhile tumor immunity is an important factor affecting the invasion and metastasis of cancer cells. In the previous studies, the applicant firstly found that as a key polarization regulatory protein, aPKC-ι was overexpressed in cholangiocarcinoma and metastatic tissue, and preliminarily found that aPKC-ι expression levels were correlate with Treg cell infiltration and TGF-β1 and IL-2 levels. Furthermore, the expression levels of aPKC-ι were also associated with Snail1. Based on the above statements, we infer that cholangiocarcinoma cell polarization regulated by aPKC-ι/Snail1 signaling pathway affect Treg cell function, and mediates cancer cell invasion and metastasis. This project intends to establish the polarization movement experimental model of the invasion and metastasis of cholangiocarcinoma cells in vitro, studies the regulation of the polarization state of cholangiocarcinoma cells and its effects on Treg cell function when aPKC-ι overexpressed or inactived, investigates the molecular mechanisms of aPKC-ι regulating Snail1, and studies the effects on invasion and metastasis by interfering aPKC-ι/ Snail1 signaling pathway. The project is expected to clarify the molecular mechanisms on invasion and metastasis of cholangiocarcinoma cells from a new perspective and it suggests us a new therapeutic approach for the treatment of cholangiocarcinoma.