BAP1 promotes breast cancer cell proliferation and metastasis by deubiquitinating KLF5

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...

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Bibliographic Details
Published in:Nature communications 2015-09, Vol.6 (1), p.8471-8471, Article 8471
Main Authors: Qin, Junying, Zhou, Zhongmei, Chen, Wenlin, Wang, Chunyan, Zhang, Hailin, Ge, Guangzhe, Shao, Ming, You, Dingyun, Fan, Zhixiang, Xia, Houjun, Liu, Rong, Chen, Ceshi
Format: Article
Language:English
Subjects:
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Breast Neoplasms - physiopathology
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Female
Humans
Kruppel-Like Transcription Factors - genetics
Kruppel-Like Transcription Factors - metabolism
Neoplasm Metastasis
Protein Binding
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
Ubiquitin Thiolesterase - genetics
Ubiquitin Thiolesterase - metabolism
Ubiquitination
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Summary: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.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms9471