USP17 Suppresses Tumorigenesis and Tumor Growth through Deubiquitinating AEP

doi:10.7150/ijbs.30106

	USP17 Suppresses Tumorigenesis and Tumor Growth through Deubiquitinating AEP
	Chen, Xi 2; Wang, Chen3 ; Liao, Keman 1; Zhou, Sunhai 1; Cao, Lu 4; Chen, Jiayi 4; Xu, Cheng 4; Lin, Yingying 1
	2019
发表期刊	INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
ISSN	1449-2288
卷号	15 期号:4 页码:738-748
发表状态	已发表
DOI	10.7150/ijbs.30106
摘要	Ubiquitin-specific protease 17 (USP17), a novel member of deubiquitinase, is reported to play essential roles in several solid tumors. However, the expression and function of USP17 in breast cancer tumorigenesis remains ambiguity. Here we found that the mRNA level of USP17 was lower in breast cancer tissues than normal tissues. Meanwhile, higher USP17 level was detected in normal epithelial cell MCF-10A and a less-malignant cell MCF-7 than malignant cell line MDA-MB-231. Inhibition of USP17 in MCF7 cells enhanced tumorigenesis and tumor growth while overexpression of USP17 in malignant MDA-MB-231 cells reduced its tumorigenesis and growth ability in vitro and in vivo. Further study revealed that USP17 interacted with and deubiquitinated Asparaginyl endopeptidase (AEP), resulting in decreased protein levels of AEP. Moreover, knockdown of AEP inhibited breast cancer tumorigenesis and growth in vitro and in vivo through the inactivation of ERK signaling. Taken together, our works indicate that USP17 deubiquitinates AEP, down-regulates its protein level, and inhibits breast cancer tumorigenesis through disturbing ERK signaling. Thus, our data suggests that USP17 is a potential tumor suppressor in breast cancer and AEP is a promising target in breast cancer therapy.
关键词	Breast cancer AEP USP17 Deubiquitination ERK
收录类别	SCI ; SCIE
语种	英语
资助项目	China Postdoctoral Science Foundation[2017M611633]
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS类目	Biochemistry & Molecular Biology ; Biology
WOS记录号	WOS:000467209800002
出版者	IVYSPRING INT PUBL
WOS关键词	LEGUMAIN EXPRESSION ; ASPARAGINE ENDOPEPTIDASE ; ENZYME USP17 ; UBIQUITIN ; CLONING ; CHAINS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/40875
专题	免疫化学研究所_特聘教授组_干细胞生物学实验室
通讯作者	Xu, Cheng; Lin, Yingying
作者单位	1.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Neurosurg, Shanghai 200127, Peoples R China 2.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Key Lab Tissue Microenvironm & Tumor, Shanghai Inst Nutr & Hlth,Shanghai Inst Biol Sci, Shanghai 200025, Peoples R China 3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 4.Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Radiat Oncol, Shanghai 200025, Peoples R China
推荐引用方式 GB/T 7714	Chen, Xi,Wang, Chen,Liao, Keman,et al. USP17 Suppresses Tumorigenesis and Tumor Growth through Deubiquitinating AEP[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2019,15(4):738-748.
APA	Chen, Xi.,Wang, Chen.,Liao, Keman.,Zhou, Sunhai.,Cao, Lu.,...&Lin, Yingying.(2019).USP17 Suppresses Tumorigenesis and Tumor Growth through Deubiquitinating AEP.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,15(4),738-748.
MLA	Chen, Xi,et al."USP17 Suppresses Tumorigenesis and Tumor Growth through Deubiquitinating AEP".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 15.4(2019):738-748.