胰腺癌化疗耐药是引起患者预后差的重要原因。本课题组研究发现FAT10可促进肿瘤的发生发展（Cancer Research，Hepatology），但其在胰腺癌化疗耐药中的作用及机制还不清楚。研究报道FOXM1与肿瘤化疗耐药密切相关。预实验发现：胰腺癌组织中FAT10与FOXM1高表达且呈正相关；在胰腺癌细胞中下调FAT10可降低FOXM1的表达，并抑制肿瘤细胞EMT发生和增强细胞对吉西他滨的敏感性。另外，抑制泛素蛋白酶体降解可阻断FAT10对FOXM1的调控，说明FAT10参与了FOXM1的泛素化降解。据此，我们推测FAT10通过抑制FOXM1的泛素化降解从而诱导EMT促进胰腺癌化疗耐药。本研究拟从临床病理、动物、细胞和分子水平，采用免疫组化、Western blot、免疫共沉淀和体外泛素化等方法，探讨FAT10在胰腺癌化疗耐药中的作用及机制。本研究将为调节胰腺癌化疗耐药提供新的理论基础。

Chemotherapy resistance is thought to be an important cause of poor prognosis in pancreatic cancer(PC).Our previous studies have shown that FAT10 could promote tumor tumorigenesis and progression(Cancer Research,Hepatology),but its role and mechanism in chemotherapy resistance of PC remain unclear. The studies have showed that FOXM1 was closely related to chemotherapy resistance of tumors.Our preliminary results found that FAT10 and FOXM1 expression were both upregulated and positively correlated in PC tissues.Knockdown of FAT10 could decrease the FOXM1 expression and inhibit EMT of PC cells，and enhance the sensitivity of PC cells to gemcitabine. Additionly, inhibition of ubiquitin-proteasome degradation could block FAT10-mediated regulation of FOXM1 expression.The results suggest that FAT10 was involved in the degradation of FOXM1.Therefore, we speculated that FAT10 promotes EMT and chemoresistance by repressing FOXM1 ubiquitination and degradation in PC cells. To confirm this hypothesis,in this study, the role and mechanism of FAT10 in chemotherapy resistance of PC will be explored at clinicopathological, animal, cellular and molecular levels by immunohistochemistry, Western blot, immunoprecipitation and in vitro ubiquitination assays. This study will provide a new theoretical basis for regulation of chemotherapy resistance in PC.