胰腺癌的高转移性是其预后差的主要原因。通过对胰腺癌临床组织样本进行高通量测序，我们鉴定出一种在高转移人群中特异性高表达的蛋白syntenin。Syntenin是一种胞内衔接蛋白，主要依赖于其PDZ结构域影响胞内蛋白质转运、蛋白质定位、转录因子激活等多种生物功能；然而在胰腺癌中尚无syntenin相关报导。我们前期通过CRISPR/Cas9敲除及激活系统成功构建了syntenin敲除及过表达细胞系。通过预实验发现胰腺癌的侵袭迁移能力明显受syntenin调控。同时，我们发现YAP1这一促进胰腺癌恶性表型的蛋白其表达量显著受syntenin调控并与syntenin存在蛋白间相互结合，而YAP1蛋白结构中存在PDZ结合模体。基于测序及预实验结果，本项目拟通过临床样本分析，动物实验，细胞实验和分子实验等探讨syntenin在胰腺癌中的功能及分子机制，并为临床胰腺癌的治疗提供新策略。

Pancreatic cancer is characterized by pronounced potential for migration, invasion, and epithelial-to-mesenchymal transition, which are the major reasons for the high mortality of this type of cancer. In our preliminary study, we identified syntenin, an oncogene specifically expressed in the tumor tissue of high metastasis patients, by high throughput sequencing of clinical tissue sampling of pancreatic cancer.. Syntenin (syndecan-binding protein, SDCBP) is a member of the PDZ domain-containing family and plays a vital role in diverse physiological processes, such as protein trafficking, nucleus import and export, and activation of transcription factors mainly through its two PDZ domains. However, little has been reported about the role of syntenin in pancreatic cancer. Stable cell lines with syntenin knockout and activation were set up through CRISPR/Cas9. In preliminary study, syntenin was found overexpressed in pancreatic cancer tissue and cell lines and promoted cancer cell invasion and migration. Furthermore, the expression of YAP1 was regulated by syntenin and can form protein complex structures with syntenin. Syntenin has two PDZ binding domains with large numbers of interacting ligands, and YAP1 has the domain of the PDZ-binding motif. We propose that syntenin can directly bind to YAP1 to stabilize YAP1 protein expression and regulate nuclear -cytoplasm localization. . The role of syntenin in inducing invasion, migration, and metastasis in pancreatic cancer is also investigated by in vivo and in vitro studies. Western, RT-QPCR, IHC, ICC, Co-IP, GST pulldown, Ch-IP, and 8×GTIIC-TEAD luciferase assay are used to determine the molecular mechanisms that regulate the interaction between syntenin and YAP1. This study can offer a new mechanism of pancreatic cancer metastasis and provide scientific basis for the development of novel treatment strategies for patients with pancreatic cancer.