果糖-1,6 -二磷酸酶1（FBP1）是糖异生途径中的重要限速酶，但其作为肿瘤抑制因子与胰腺癌进展的关系尚不清楚。我们前期研究发现胰腺癌中FBP1低表达提示不良预后，且质谱结果提示FBP1可以与糖基化酶OGT/去糖基化酶OGA相互作用。目前尚没有FBP1糖基化修饰功能研究的报道，为此，我们提出假设，胰腺癌中的缺氧环境可以诱导OGT/OGA与FBP1作用模式发生变化，促进FBP1糖基化修饰并发生降解/功能失活，导致肿瘤代谢速率增加，最终加快胰腺癌进展。为了验证该假说，我们将通过胰腺癌细胞系及胰腺癌组织，从分子、细胞、组织以及动物整体水平等多方面探讨FBP1在胰腺癌进展中的重要作用，明确低氧条件下OGT/OGA通过诱导FBP1糖基化修饰以及对FBP1蛋白功能的调控机制。本研究将从FBP1糖基化这个新视点揭示胰腺癌肿瘤代谢新机制，为未来代谢靶向治疗提供新思路。

Fructose -1,6 biphosphatase 1 (FBP1) is an important rate-limiting enzyme in gluconeogenesis.However, the function of FBP1 as tumor suppressor and its relationship with pancreatic cancer are still unclear. Our previous study suggested that the low expression of FBP1 in pancreatic cancer was associated with a poor prognosis and mass spectrum result indicated FBP1 may interact with the glycosylation enzyme OGT/ deglycosylase OGA. Therefore, we propose the hypothesis that hypoxia can induce the interaction change between OGT/OGA and FBP1 in pancreatic cancer cells, which promotes FBP1 glycosylation and degradation/inactivation, leads to increase the tumor metabolic rate and ultimately acceleratesthe progression of pancreatic cancer. In order to verify this hypothesis, we used pancreatic cancer cell lines and tissues to explore the important role of FBP1 in the progression of pancreatic cancer from the aspects of molecular, cell and tissue and animal levels. Besides, we also want to figure out the underlying mechanism of FBP1 protein function change regulated by glycosylation modification induced by OGT/OGA under hypoxia condition. This study will reveal new mechanisms of pancreatic cancer metabolism, which could provide new ideas about metabolic therapeutic targets in the future treatment of pancreatic cancer.