Deubiquitinase ubiquitin-specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells

doi:10.1111/cas.13953

	Deubiquitinase ubiquitin-specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells
	Lu, Qin 4,5; Lu, Dayun 6; Shao, Zhi-Ming 1,2,3,4,5,7; Li, Da-Qiang 1,2,3,4,5,7
刊名	CANCER SCIENCE
	2019-04-01
卷号	110 期号:4 页码:1268-1278
关键词	breast cancer deubiquitinating enzyme E3 ubiquitin ligase ring finger protein 115 ubiquitin-specific protease 9X
ISSN号	1347-9032
DOI	10.1111/cas.13953
通讯作者	Shao, Zhi-Ming(zhimingshao@fudan.edu.cn) ; Li, Da-Qiang(daqiangli1974@fudan.edu.cn)
英文摘要	The E3 ubiquitin ligase ring finger protein 115 (RNF115) is overexpressed in more than half of human breast tumors and is implicated in the pathogenesis and progression of breast cancer. However, the mechanism behind RNF115 overexpression in breast tumors remains largely unknown. Here we report that ubiquitin-specific protease 9X (USP9X), a substrate-specific deubiquitinating enzyme, stabilizes RNF115 and thereby regulates its biological functions in breast cancer cells. Immunoprecipitation and GST pull-down assays showed that USP9X interacted with RNF115. Depletion of RNF115 by siRNAs or overexpression of RNF115 did not significantly affect USP9X expression. In contrast, knockdown of USP9X in breast cancer cells by siRNAs reduced RNF115 protein abundance, which was partially restored following treatment with proteasome inhibitor MG-132. Moreover, depletion of USP9X reduced the half-life of RNF115 and increased its ubiquitination. Conversely, overexpression of USP9X resulted in an accumulation of RNF115 protein, accompanied by a decrease in its ubiquitination. RNF115 mRNA levels were unaffected by overexpression or knockdown of USP9X. Furthermore, USP9X protein expression levels correlated positively with RNF115 in breast cancer cell lines and breast tumor samples. Importantly, reintroduction of RNF115 in USP9X-depleted cells partially rescued the reduced proliferation, migration, and invasion of breast cancer cells by USP9X knockdown. Collectively, these findings indicate that USP9X is a stabilizer of RNF115 protein and that the USP9X-RNF115 signaling axis is implicated in the breast cancer malignant phenotype.
资助项目	National Natural Science Foundation of China[81572584] ; National Natural Science Foundation of China[81772805] ; Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning[2013-06] ; Science and Technology Innovation Action Plan of Shanghai Municipal Science and Technology Commission[16JC1405400] ; Fudan University
WOS关键词	DEUBIQUITYLATING ENZYMES ; USP9X ; SUPPRESSES ; INHIBITION ; GROWTH ; BCA2 ; TUMORIGENESIS ; DEGRADATION ; METASTASIS ; ACTIVATION
WOS研究方向	Oncology
语种	英语
出版者	WILEY
WOS记录号	WOS:000467640800013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289841]
专题	中国科学院上海药物研究所
通讯作者	Shao, Zhi-Ming; Li, Da-Qiang
作者单位	1.Fudan Univ, Shanghai Med Coll, Key Lab Breast Canc Shanghai, Shanghai, Peoples R China 2.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China 3.Fudan Univ, Shanghai Med Coll, Dept Breast Surg, Shanghai, Peoples R China 4.Fudan Univ, Shanghai Med Coll, Shanghai Canc Ctr, Shanghai, Peoples R China 5.Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Shanghai, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, CAS Key Lab Receptor Res, Shanghai, Peoples R China 7.Fudan Univ, Shanghai Med Coll, Inst Canc, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Lu, Qin,Lu, Dayun,Shao, Zhi-Ming,et al. Deubiquitinase ubiquitin-specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells[J]. CANCER SCIENCE,2019,110(4):1268-1278.
APA	Lu, Qin,Lu, Dayun,Shao, Zhi-Ming,&Li, Da-Qiang.(2019).Deubiquitinase ubiquitin-specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells.CANCER SCIENCE,110(4),1268-1278.
MLA	Lu, Qin,et al."Deubiquitinase ubiquitin-specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells".CANCER SCIENCE 110.4(2019):1268-1278.