Abstract 4967: The BAP1 deubiquitinase promotes triple-negative breast cancer partially by stabilizing the KLF5 transcription factor

Abstract The transcription factor KLF5 is highly expressed in basal triple-negative breast cancer (TNBC) and promotes breast cancer cell proliferation, survival and tumor growth. However, the mechanism by which KLF5 is regulated in breast cancer remains unclear. In this study, we performed a genome-wide siRNA library screening against deubiquitinases (DUBs) and identified BAP1 as a bona fide KLF5 DUB. BAP1 interacts with KLF5 directly 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 partially rescued by ectopic KLF5 expression. Collectively, our findings not only identified BAP1 as the first DUB for KLF5 but also revealed a critical mechanism for KLF5 expression regulation in TNBC. BAP1 could be a potential therapeutic target for TNBC and other cancers. Citation Format: Ceshi Chen, Junying Qin, Zhongmei Zhou. The BAP1 deubiquitinase promotes triple-negative breast cancer partially by stabilizing the KLF5 transcription factor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4967. doi:10.1158/1538-7445.AM2015-4967