上皮间质转化（EMT）是胰腺癌细胞获得侵袭转移潜能、导致预后极差的主要原因，近年来研究提示，EMT与糖酵解相关。我们前期研究发现：EMT受糖酵解调控，SIRT3→E-cadherin是其中一条重要的信号通路；EMT反过来也可以调控糖酵解，E-cadherin/β-catenin→SIRT3信号通路可能参与了其中，由此提出“EMT-糖酵解”反馈环路中E-cadherin/SIRT3功能轴的存在。本项目拟围绕此功能轴进一步开展以下研究：①分析E-cadherin、β-catenin和SIRT3之间的关系，对功能轴进行验证；②阐明此功能轴对“EMT-糖酵解”反馈环路的影响；③通过体内外实验干预此功能轴，为胰腺癌侵袭转移的治疗提供潜在靶点。

Epithelial-mesenchymal transition (EMT) renders metastasis potentials to pancreatic cancer cells and is associated with poor prognosis. Evidence has indicated that EMT is associated with glycolytic process. Our previous study revealed that: EMT could be regulated by glycolysis, which required the regulation of SIRT3→E-cadherin signaling pathway; moreover, EMT also regulated glycolysis through E-cadherin/β-catenin→SIRT3 signaling pathway, thus we put forward the physiological existence of E-cadherin/SIRT3 axis in the “EMT-glycolysis” feedback loop. According to the above mentioned clues, we plan to carry out the following studies:①Verification of the E-cadherin/SIRT3 axis through analysis of the regulatory roles between E-cadherin、β-catenin and SIRT3; ②Elucidating the influence of E-cadherin/SIRT3 axis on the “EMT-glycolysis” feedback loop; ③ Carrying out in vivo and in vitro experiments to intervene the E-cadherin/SIRT3 axis with the aim of providing therapeutic targets to inhibit metastasis of pancreatic cancer.