膜结合型粘蛋白MUC4是胰腺癌特异性分子，由多个功能结构域组成。其中NIDO、AMOP和vWD是在所有膜结合型粘蛋白中唯MUC4所独有的结构域。本课题组前期工作表明， NIDO区与胰腺癌细胞的抗凋亡功能及侵袭转移密切相关。在用计算机模拟研究分子之间相互作用和预实验的基础上，我们提出"MUC4独有的保守而重要的三个结构域可能通过与肿瘤微环境中的基质蛋白、细胞表面分子的相互作用，介导胰腺癌特征性肿瘤学行为-转移和嗜神经浸润"。本项目将立足前期基础，应用缺失突变、免疫共沉淀、石英晶体微量天平、基因芯片、体内体外胰腺癌神经浸润模型、活体成像等技术证明此假说，并阐明其相关分子机制，从而深化对MUC4及其独特结构域功能的认识，为寻找并阻断胰腺癌转移及复发的特异性靶点奠定基础，对改善胰腺癌的预后具有重要意义。

MUC4, one of membrane-bound mucins, is the specific molecule of pancreatic cancer (PC) which consists of a number of domains. Among all the membrane-bound mucins, MUC4 is the only one found to contain NIDO, AMOP and vWD domains. Our previous study showed that NIDO was associated with metastasis and anti-apoptosis of PC. After combining preliminary experiments and assay of molecular interaction with computer technology, we hypothesize that the three conservative and specific domains of MUC4 induce metastasis and perineural invasion of PC, which seem to be two significant features of PC, via interacting with extracellular matrix and/or cell surface molecules in the microenvironment of PC. This project is intended to validate the hypothesis and investigate the underlying mechanisms by means of deletion mutant, co-immunoprecipitation, QCM, microarray, animal models of PNI, vital fluorescence imaging etc. This study will provide deeper insights into the function of MUC4 and its specific domains, and contribute to finding the therapeutic target of PC based on underlying mechanisms, which is of great significance for the improvement of PC prognosis.