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Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway

文献类型：期刊论文

作者Xu, Qi1,2,4; Wu, Ning2,4; Li, Xiangqian1,5; Guo, Chuanlong1,2,4; Li, Chao1,2,4; Jiang, Bo2,4; Wang, Huaizhi3; Shi, Dayong1,5
刊名CELL DEATH & DISEASE
出版日期2019-11-19
卷号10页码:15
ISSN号2041-4889
DOI10.1038/s41419-019-2073-4
通讯作者Wang, Huaizhi(whuaizhi@gmail.com) ; Shi, Dayong(shidayong@sdu.edu.cn)
英文摘要Pancreatic cancer is a highly malignant cancer and lacks effective therapeutic targets. Protein-tyrosine phosphatase 1B (PTP1B), a validated therapeutic target for diabetes and obesity, also plays a critical positive or negative role in tumorigenesis. However, the role of PTP1B in pancreatic cancer remains elusive. Here, we initially demonstrated that PTP1B was highly expressed in pancreatic tumors, and was positively correlated with distant metastasis and tumor staging, and indicated poor survival. Then, inhibition of PTP1B either by shRNA or by a specific small-molecule inhibitor significantly suppressed pancreatic cancer cell growth, migration and colony formation with cell cycle arrest in vitro and inhibited pancreatic cancer progression in vivo. Mechanism studies revealed that PTP1B targeted the PKM2/AMPK/mTOC1 signaling pathway to regulate cell growth. PTP1B inhibition directly increased PKM2 Tyr-105 phosphorylation to further result in significant activation of AMPK, which decreased mTOC1 activity and led to inhibition of p70S6K. Meanwhile, the decreased phosphorylation of PRAS40 caused by decreased PKM2 activity also helped to inhibit mTOC1. Collectively, these findings support the notion of PTP1B as an oncogene and a promising therapeutic target for PDAC.
资助项目National Natural Science Foundation of China[81872906] ; National Natural Science Foundation of China[81703354] ; National Natural Science Foundation of China[81672382] ; National key R&D Program of China[2017YFC1308600] ; CAS[QYZDB-SSW-DQC014] ; National Program for Support of Top-notch Young Professionals ; Fund of Taishan scholar project ; Shandong Provincial Natural Science Foundation for Distinguished Young Scholars[JQ201722] ; NSFC-Shandong Joint Fund[U1706213] ; Qingdao Marine Biomedical Science and Technology Innovation Center[2017-CXZX01-1-1] ; Qingdao Marine Biomedical Science and Technology Innovation Center[2017-CXZX01-3-9] ; Key research and development project of Shandong province[2018GSF118200]
WOS研究方向Cell Biology
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000497972900001
源URL[http://ir.qdio.ac.cn/handle/337002/163870]  
专题海洋研究所_实验海洋生物学重点实验室
通讯作者Wang, Huaizhi; Shi, Dayong
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao, Shandong, Peoples R China
3.Univ Chinese Acad Sci, Chongqing Gen Hosp, Inst Hepatopancreatobiliary Surg, Chongqing 401147, Peoples R China
4.Chinese Acad Sci, Inst Oceanol, Ctr Ocean Mega Sci, Key Lab Expt Marine Biol, Qingdao, Shandong, Peoples R China
5.Shandong Univ, State Key Lab Microbial Technol, Jinan 250100, Shandong, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Qi,Wu, Ning,Li, Xiangqian,et al. Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway[J]. CELL DEATH & DISEASE,2019,10:15.
APA Xu, Qi.,Wu, Ning.,Li, Xiangqian.,Guo, Chuanlong.,Li, Chao.,...&Shi, Dayong.(2019).Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway.CELL DEATH & DISEASE,10,15.
MLA Xu, Qi,et al."Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway".CELL DEATH & DISEASE 10(2019):15.

入库方式： OAI收割

来源：海洋研究所

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