胆道癌是一种罕见却高致命的恶性肿瘤。目前，胆道癌的某个分子靶点决定其高度的侵略性质仍然未明。研究表明，细胞间粘附缺失是肿瘤侵袭转移的先决条件，上皮-间质转化( EMT)作为一种肿瘤侵袭转移的分子作用机制，与伴随的蛋白酶一起断裂黏着连接和桥粒的完整性，提示桥粒组件异常与EMT及伴随的蛋白酶密切相关。桥粒芯糖蛋白-2(Dsg-2)是细胞间粘附成分之一，然而在胆道癌中的生物学作用及其机制尚未清楚。本研究拟应用蛋白表达分析技术，分析Dsg2表达与临床病理学参数之间的相互关系来评估其临床意义；体外应用腺病毒、shRNA技术特异性过表达/沉默胆道癌细胞Dsg2表达，正反两方面分析其生物学功能及对EMT相关基因及伴随的蛋白酶表达调控关系或细胞内传导通路；建立小鼠胆道癌模型，证实Dsg2通过调控EMT导致肿瘤演进。研究将阐明Dsg2抑制胆道癌侵袭转移的分子机制，可为胆道癌提供新的预后因子及治疗靶点。

Biliarry tract cancer (BTC) is a rare but highly fatal malignancy. To date, molecular targets of BTC that determine its highly aggressive nature remain unidentified. Loss of cell-cell adhesion is a prerequisite for the tumor invasion and metastasis. Epithelial–mesenchymal transition (EMT) is one of molecular mechanism of tumor invasion and metastasis. EMT with accompanied proteases disrupt of adherent junctions and desmosomal integrity. These indicate the abnormality of desmosome components is closely related to the EMT and the proteases. Desmoglein2 (Dsg2) is one of the components of the cell–cell adherence junction. However, the biological role of BTC and its mechanism is not yet clear. In this study, we will investigate the the clinical significance of Dsg2 by using protein expression technology and clinical pathologic characteristics. Dsg2 is up/down-regulated by adenovirus/shRNA in human BTC cells, to look at the positive and negative aspects of Dsg2 on the EMT and the accompanied proteases or involved in cellular signal transduction pathways, as well as biological functions. The hypothesis will be confirmed by BTC animal model. In this study, we will clarify the molecular mechanism of Dsg2 on suppression of invasion and metastasis of BTC, will provide a new prognostic factor and therapeutic target for BTC.