单位：[1]Organ Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China手术科室器官移植中心四川省人民医院[2]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China华中科技大学同济医学院附属协和医院[3]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China华中科技大学同济医学院附属同济医院外科学系骨科
Pancreatic ductal adenocarcinoma (PDAC) is considered to be the deadliest cancer type in the world. Chemotherapy resistance, including gemcitabine, is the main reason for poor prognosis in PDAC patients. Increased aerobic glycolysis is involved in chemotherapy resistance in PDAC. Fructose-1,6-bisphosphatase (FBP1) is one of the key enzymes in the process of gluconeogenesis and negatively regulates aerobic glycolysis. FBP1 loss is common in PDAC patient specimens and is associated with gemcitabine resistance by activating the MAPK pathway. While the regulatory mechanism of FBP1 in pancreatic cancer remains un-elucidated. Here, we found that ubiquitin-specific protease 44 (USP44) was down-regulated in PDAC patients, and USP44 might be a prognostic marker for PDAC patients. USP44 inhibit tumor cells progression and regulated gemcitabine resistance in PDAC. Importantly, we revealed USP44 promoted FBP1 deubiquitination to increase FBP1 protein expression in pancreatic cancer, which might be one of the underlying mechanisms of USP44 impeding the progression of pancreatic cancer. Collectively, the recognition of USP44 in the stabilization of FBP1 indicates USP44 might be considered as a new prognostic marker for pancreatic cancer therapy.
基金：
This work was supported by grants from the Chinese National Natural Science Foundation Grant No. 81702374.
第一作者单位：[1]Organ Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
通讯作者：
通讯机构：[2]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China[3]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China[*1]Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.[*2]Department of Orthopedics,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China.
推荐引用方式(GB/T 7714)：
Chong Yang,Shikai Zhu,Hongji Yang,et al.USP44 suppresses pancreatic cancer progression and overcomes gemcitabine resistance by deubiquitinating FBP1.[J].American journal of cancer research.2019,9(8):1722-1733.
APA：
Chong Yang,Shikai Zhu,Hongji Yang,Sisi Deng,Ping Fan...&Xin Jin.(2019).USP44 suppresses pancreatic cancer progression and overcomes gemcitabine resistance by deubiquitinating FBP1..American journal of cancer research,9,(8)
MLA：
Chong Yang,et al."USP44 suppresses pancreatic cancer progression and overcomes gemcitabine resistance by deubiquitinating FBP1.".American journal of cancer research 9..8(2019):1722-1733
