胆囊癌是胆道系统最常见的恶性肿瘤，早期发生侵袭转移是其预后差最主要原因。上皮间质转换（EMT）是上皮细胞来源的恶性肿瘤细胞获得侵袭转移能力的重要生物学过程。本课题组前期研究发现，利用RNAi技术沉默Nemo样激酶（NLK）可以使EMT相关蛋白表达水平发生变化，提示NLK参与了胆囊癌的EMT过程，进一步通过酵母双杂交实验，筛选出NLK的相互作用蛋白Paxillin。在此基础上，我们提出假设：NLK通过与paxillin蛋白相互作用后诱导了胆囊癌细胞发生EMT。针对于此，本项目拟通过分子生物学、细胞生物学及实验动物模型等手段，明确NLK蛋白与Paxillin蛋白的相互作用机制，揭示其在调控EMT及胆囊癌转移过程中的功能和相关分子的调控机制。通过阐明NLK功能和分子机制，可进一步深入对胆囊癌转移相关特征性的分子调控网络的理解，为下一步相应治疗策略的开发及改善胆囊癌患者的预后提供新的理论依据。

Gallbladder carcinoma (GBC) is the most aggressive malignancy of the biliary tract. GBC has an extremely poor prognosis because of its early metastasis. Epithelial-mesenchymal transitions (EMT) is an important biological process in which epithelial malignancies can obtain ability of invasion and metastasis. In our previous research, we identified that silencing Nemo-like kinase (NLK) expression by RNAi technique can change the level of EMT related proteins, which indicated that NLK was involved in the EMT process of GBC. We further screened that Paxillin is the interactive proteins of NLK by Yeast Two-Hybrid. Our previous data strongly suggested that NLK induces EMT in GBC cells through the interaction with Paxillin protein. In this project, we plan to investigate the functions and molecular mechanisms of EMT regulated by NLK and Paxillin via molecular biology, cellular biology and in vivo animal models. The completion of this project might contribute to clarify the molecular regulatory networks related to the metastasis in GBC, and provide the theoretical basis for developing the corresponding treatment strategies and improving the prognosis of patients with GBC.