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Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway
Xu, Qi1,2,3; Wu, Ning1,2; Li, Xiangqian3,4; Guo, Chuanlong1,2,3; Li, Chao1,2,3; Jiang, Bo1,2; Wang, Huaizhi5; Shi, Dayong3,4
2019-11-19
Source PublicationCELL DEATH & DISEASE
ISSN2041-4889
Volume10Pages:15
Corresponding AuthorWang, Huaizhi(whuaizhi@gmail.com) ; Shi, Dayong(shidayong@sdu.edu.cn)
AbstractPancreatic 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.
DOI10.1038/s41419-019-2073-4
Indexed BySCI
Language英语
Funding ProjectNational 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 Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000497972900001
PublisherNATURE PUBLISHING GROUP
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.qdio.ac.cn/handle/337002/163871
Collection实验海洋生物学重点实验室
Corresponding AuthorWang, Huaizhi; Shi, Dayong
Affiliation1.Chinese Acad Sci, Inst Oceanol, Ctr Ocean Mega Sci, Key Lab Expt Marine Biol, Qingdao, Shandong, Peoples R China
2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Drugs & Bioprod, Qingdao, Shandong, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
4.Shandong Univ, State Key Lab Microbial Technol, Jinan 250100, Shandong, Peoples R China
5.Univ Chinese Acad Sci, Chongqing Gen Hosp, Inst Hepatopancreatobiliary Surg, Chongqing 401147, Peoples R China
First Author AffilicationInstitute of Oceanology, Chinese Academy of Sciences
Recommended Citation
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.
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