机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Collaborative Innovation Center for Cancer Medicine, Kunming, Yunnan 650223, China.[2]Graduate School of the Chinese Academy of Sciences, Beijing 100039, China.[3]Department of Breast Surgery, Breast Cancer Clinical Research Center, Cancer Hospital, Kunming Medical University, Kunming, Yunnan 650031, China.[4]Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.医技科室病理科昆明医科大学附属第一医院[5]Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.昆明医科大学附属第一医院[6]Kunming Medical University, Kunming, Yunnan 650031, China.
The transcription factor KLF5 is highly expressed in basal-like breast cancer and promotes breast cancer cell proliferation, survival, migration and tumour growth. Here we show that, in breast cancer cells, KLF5 is stabilized by the deubiquitinase (DUB) BAP1. With a genome-wide siRNA library screen of DUBs, we identify BAP1 as a bona fide KLF5 DUB. BAP1 interacts directly with KLF5 and stabilizes KLF5 via deubiquitination. KLF5 is in the BAP1/HCF-1 complex, and this newly identified complex promotes cell cycle progression partially by inhibiting p27 gene expression. Furthermore, BAP1 knockdown inhibits tumorigenicity and lung metastasis, which can be rescued partially by ectopic expression of KLF5. Collectively, our findings not only identify BAP1 as the DUB for KLF5, but also reveal a critical mechanism that regulates KLF5 expression in breast cancer. Our findings indicate that BAP1 could be a potential therapeutic target for breast and other cancers.
基金：
This study was supported by the National Key Basic Research
Program of China (2013CB910900), the Strategic Priority Research Program of the
Chinese Academy of Sciences, Stem Cell and Regenerative Medicine Research
(XDA01040406) and the National Natural Science Foundation of China (81120108019,
81325016 and U1132605).
第一作者机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Collaborative Innovation Center for Cancer Medicine, Kunming, Yunnan 650223, China.[2]Graduate School of the Chinese Academy of Sciences, Beijing 100039, China.
通讯作者：
推荐引用方式(GB/T 7714)：
Junying Qin,Zhongmei Zhou,Wenlin Chen,et al.BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5[J].NATURE COMMUNICATIONS.2015,6:doi:10.1038/ncomms9471.
APA：
Junying Qin,Zhongmei Zhou,Wenlin Chen,Chunyan Wang,Hailin Zhang...&Ceshi Chen.(2015).BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5.NATURE COMMUNICATIONS,6,
MLA：
Junying Qin,et al."BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5".NATURE COMMUNICATIONS 6.(2015)
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