引发快速的肿瘤转移是胰腺癌死亡的关键因素，是胰腺癌治疗的难点。我们首次发现蛋白P311在胰腺癌组织中特异性高表达，促进胰腺癌细胞的上皮-间质转化(EMT)和迁移侵袭能力。进一步研究发现P311可显著增强调节EMT的Periostin的翻译效率，在胰腺癌组织中与Periostin的表达显著正相关，并且敲低Periostin可显著抑制P311促进的EMT。因此，我们提出P311通过上调Periostin的翻译，促进EMT，进而引发胰腺癌细胞的转移。本项目拟运用多聚核糖体分离、点击化学、RIP技术、EMSA等方法证明胰腺癌细胞中P311与Periostin mRNA直接结合，P311与Periostin的5’UTR区域的结合位点，该结合促进Periostin的翻译；同时结合小鼠胰腺癌肿瘤模型，证明P311-Periostin轴在促进胰腺癌转移中的重要作用，为理解胰腺癌转移机制提供新的线索。

Fast metastasis is the primary cause of pancreatic cancer (PC) related deaths and the difficulty for treatment. We firstly show that P311 get higher expression in pancreatic tumors than in surrounding normal pancreas. High expression of P311 promotes epithelial-to-mesenchymal transition (EMT) in PC cells and also enhances their migration and invasion ability. Our further studies show that P311 can promote the translational efficiency of EMT inducer Periostin, and the expression of Periostin is positively regulated by P311. Moreover, siRNA-induced knockdown of Periostin can reverse P311-mediated epithelial-to-mesenchymal transition in PC cells. Here, in this program, we decide to elucidate the mechanism of translational activation of Periostin by P311 and the central role of P311-Periostin axis in the regulation of PC metastasis by promoting Periostin translation, utilizing polysome profiling, CLICK chemistry, RNA Binding Protein Immunoprecipitation Assay and EMSA, together with PC mice models. Collectively, findings from our studies will provide new clues for understanding mechanism of PC metastasis.