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

doi:10.1038/s41419-019-2073-4

IOCAS-IR > 实验海洋生物学重点实验室

	Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway
	Xu, Qi 1,2,3; Wu, Ning 1,2; Li, Xiangqian 3,4; Guo, Chuanlong 1,2,3; Li, Chao 1,2,3; Jiang, Bo 1,2; Wang, Huaizhi 5; Shi, Dayong 3,4
	2019-11-19
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	10 页码:15
通讯作者	Wang, Huaizhi([email protected]) ; Shi, Dayong([email protected])
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.
DOI	10.1038/s41419-019-2073-4
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81872906]###3479; National Natural Science Foundation of China[81703354]###282; National Natural Science Foundation of China[81672382]###3480; National key R&D Program of China[2017YFC1308600]###3481; CAS[QYZDB-SSW-DQC014]###3046; National Program for Support of Top-notch Young Professionals###557; Fund of Taishan Scholar Project###2457; Shandong Provincial Natural Science Foundation for Distinguished Young Scholars[JQ201722]###556; NSFC-Shandong Joint Fund[U1706213]###286; Qingdao Marine Biomedical Science and Technology Innovation Center[2017-CXZX01-1-1]###3482; Qingdao Marine Biomedical Science and Technology Innovation Center[2017-CXZX01-3-9]###3483; Key research and development project of Shandong province[2018GSF118200]###284; 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
WOS类目	Cell Biology
WOS记录号	WOS:000497972900001
出版者	NATURE PUBLISHING GROUP
引用统计	被引频次：53[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.qdio.ac.cn/handle/337002/163871
专题	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.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
第一作者单位	中国科学院海洋研究所
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.

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