间质增生反应是胰腺癌的重要病理特征之一。本课题组前期研究结果显示，YAP在胰腺癌中高表达，促进胰腺癌细胞的生长及侵袭转移，同时激活下游信号通路分泌CTGF促进星状细胞活化，与间质纤维化程度呈正相关；而体外给予TGF-β1后肿瘤细胞的YAP表达显著提高。因此我们推测胰腺癌细胞中YAP通过旁分泌CTGF促进星状细胞活化，活化的星状细胞TGF-β1分泌增多作用于临近的胰腺癌细胞，使YAP表达上升，提示存在以YAP为核心的TGF-β1-YAP-CTGF功能轴调控胰腺癌细胞与胰腺星状细胞交互作用。本研究将从临床病理、细胞培养、裸鼠胰腺癌模型、LSL-KrasG12D/+; Trp53fl/+; Pdx1-Cre (KPC)转基因动物模型4个方面入手，应用分子生物学，体外细胞共培养，小动物活体成像等技术探索TGF-β1-YAP-CTGF功能轴调控胰腺癌细胞与胰腺星状细胞交互作用的机制。

Desmoplastic reaction is one of the most important pathological features of pancreatic cancer. Recently, we have found that YAP was increased in pancreatic cancer tissue and YAP could promote the growth, invasion and metastasis of pancreatic cancer cells, at the same time it could also promote PSC activation through secretion of CTGF and YAP was positively correlated with the degree of desmoplastic reaction. The YAP level was increased significantly in tumor cells after treated with TGF-β1. So we speculated that overexpression of YAP in pancreatic cancer cells could promote stellate cell activation through paracrine CTGF, and the TGF-β1 secreted by activated stellate cells will increase YAP expression in adjacent pancreatic cancer cells. So there may exist a TGF-β1-YAP-CTGF function axis regulating pancreatic cancer cell and pancreatic stellate cell interactions. To further address this hypothesis, clinical pathology information, co-culture model in vitro, nude mouse model and LSL-KrasG12D/+; Trp53fl/+; Pdx1-Cre (KPC) transgenic mouse model would be designed and lots of technologies such as molecular biology technology, Laser capture microscopic cutting, Optical in vivo Imaging technology will be conducted. This study will help us to delineate the key role of the TGF-β1-YAP-CTGF function axis in pancreatic cancer cells and pancreatic stellate cell and the molecular mechanisms of pancreatic cancer cell and pancreatic stellate cell co-couple interaction.