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The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer

文献类型：期刊论文

作者Zhou ZM1,2; Liu R2; Chen CS[*]1,2
刊名INTERNATIONAL JOURNAL OF CANCER
出版日期2012
卷号130期号:7页码:1504-1510
关键词WWP1 TRAIL caspase-8 apoptosis breast cancer
通讯作者chenc@mail.kiz.ac.cn
合作状况其它
英文摘要WW domain containing E3 ubiquitin protein ligase 1 (WWP1) is an HECT domain-containing E3 ligase regulating apoptosis. The WWP1 gene is frequently amplified and overexpressed in estrogen receptor a (ERa)-positive breast cancer. Inhibition of WWP1 by siRNA induced apoptosis in MCF7 and HCC1500. In our study, we demonstrate that WWP1 depletion by siRNA activated the extrinsic apoptotic pathway. WWP1 depletion-induced apoptosis was rescued by the overexpression of the wild-type WWP1 but not the E3 ligase inactive WWP1-C890A mutant in MCF7 cells. In contrast, WWP1-C890A enhanced apoptosis, suggesting that the E3 ligase activity is required for WWP1 to promote cell survival. The expression levels of WWP1 in four breast cancer cell lines were specifically correlated with the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) resistance, but not TNFa and doxorubicin resistance. Both WWP1 depletion and dominant negative WWP1 overexpression increased the TRAIL-induced caspase-8 recruitment and apoptosis although WWP1 did not regulate FLIP and death receptor levels. Depletion of the initial caspase-8 blocked WWP1 inhibition-induced apoptosis in MCF7. These findings suggest that inhibition of WWP1 may be combined with TRAIL to suppress ERa-positive breast cancer cell survival.
收录类别SCI
资助信息National Nature Science Foundation of China General Program; Grant number: 81072162; Grant sponsor: Yunnan Province High-Profile Talents Program; Grant number: 2010CI114; Grant sponsor: American Cancer Society; Grant number: RSG-08-199-01
语种英语
WOS记录号WOS:000299633300004
公开日期2012-03-19
源URL[http://159.226.149.42:8088/handle/353002/6872]  
专题昆明动物研究所_肿瘤生物学
昆明动物研究所_动物模型与人类重大疾病机理重点实验室
作者单位1.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China
2.The Center for Cell Biology and Cancer Research, MS355, Albany Medical College, Albany, NY
推荐引用方式
GB/T 7714		 Zhou ZM,Liu R,Chen CS[*]. The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer[J]. INTERNATIONAL JOURNAL OF CANCER,2012,130(7):1504-1510.
APA Zhou ZM,Liu R,&Chen CS[*].(2012).The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer.INTERNATIONAL JOURNAL OF CANCER,130(7),1504-1510.
MLA Zhou ZM,et al."The WWP1 ubiquitin E3 ligase increases TRAIL resistance in breast cancer".INTERNATIONAL JOURNAL OF CANCER 130.7(2012):1504-1510.

入库方式： OAI收割

来源：昆明动物研究所

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