胰腺癌是全球致死率最高的恶性肿瘤之一，5年生存率仅为1-5%。上皮间质转化和嗜神经侵袭是胰腺癌的重要特征，也是导致胰腺癌患者不良预后的主要原因之一。以往针对C型凝集素样受体CLEC-2的研究主要集中在血小板和免疫细胞中，然而CLEC-2在上皮来源组织中的表达没有报道。我们前期研究中首次发现CLEC-2在胰腺等上皮组织中有不同程度的阳性表达，然而CLEC-2是否参与胰腺癌的发生发展尚不清楚。在本项目中，我们将探讨CLEC-2在胰腺癌中的表达变化以及相关调控机制，鉴定CLEC-2在胰腺癌细胞中的信号传导通路和靶基因；同时在此基础上研究CLEC-2通路调控胰腺癌细胞上皮间质转化和嗜神经侵袭的功能机制，并验证CLEC-2阻断性抗体在抑制胰腺癌转移和嗜神经侵袭中的作用，从而为阐述糖链受体在胰腺癌发生发展中的重要作用提供新的依据，并为胰腺癌的临床治疗提供新的线索。

Pancreatic cancer is one of the most lethal of all types of cancer worldwide, with the 5-year survival rate ranging only at 1–5%. Epithelial-mesenchymal transition and perineural invasion are key features of pancreatic cancer, and also contribute to the poor prognosis of pancreatic cancer patients. Previous studies about C-type lectin-like receptor CLEC-2 focused on its roles in platelets and immune cells, while its expression in epithelial tissues remains largely unknown. Our previous research first indicated that CLEC-2 was expressed in a series of epithelial tissues including pancreas; however, whether CLEC-2 is involved in the tumorigenesis and development of pancreatic cancer is not defined. In this study, we plan to determine the expression pattern of CLEC-2 in pancreatic cancer and uncover the regulatory mechanisms of its expression. We will also identify the downstream signaling and target genes of CLEC-2 in pancreatic cancer cells, and study whether and how CLEC-2 signaling modulates epithelial-mesenchymal transition and perineural invasion of pancreatic cancer. In addition, we will explore the potential therapeutic effects of CLEC-2 blocking antibody against metastasis and perineural invasion of pancreatic cancer in vivo. Thus, our study may uncover novel mechanisms underlying the role of glycan receptors in regulating tumorigenesis and development of pancreatic cancer, and provide new strategies for the clinical treatment of pancreatic cancer.