BRD4-specific PROTAC inhibits basal-like breast cancer partially through downregulating KLF5 expression

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	BRD4-specific PROTAC inhibits basal-like breast cancer partially through downregulating KLF5 expression
	Kong, YJ; Lan, TL; Wang, LZ; Gong, C; Lv, WX; Zhang, HL; Zhou, CA; Sun, XY; Liu, WJ; Huang, HH; Weng, X; Cai, C; Peng, WF; Zhang, M; Jiang, DW; Yang, CY; Liu, X; Rao, Y; Chen, CS
	2024
发表期刊	ONCOGENE
ISSN	0950-9232
卷号	43 期号:39 页码:2914-2926
摘要	Interest in the use of proteolysis-targeting chimeras (PROTACs) in cancer therapy has increased in recent years. Targeting bromodomain and extra terminal domain (BET) proteins, especially bromodomain-containing protein 4 (BRD4), has shown inhibitory effects on basal-like breast cancer (BLBC). However, the bioavailability of BRD4 PROTACs is restricted by their non-selective biodegradability and low tumor-targeting ability. We demonstrated that 6b (BRD4 PROTAC) suppresses BLBC cell growth by targeting BRD4, but not BRD2 and BRD3, for cereblon (CRBN)-mediated ubiquitination and proteasomal degradation. Compound 6b also inhibited expression of Kr & uuml;ppel-like factor 5 (KLF5) transcription factor, a key oncoprotein in BLBC, controlled by BRD4-mediated super-enhancers. Moreover, 6b inhibited HCC1806 tumor growth in a xenograft mouse model. The combination of 6b and KLF5 inhibitors showed additive effects on BLBC. These results suggest that BRD4-specific PROTAC can effectively inhibit BLBC by downregulating KLF5, and that 6b has potential as a novel therapeutic drug for BLBC.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14563
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Kong, YJ,Lan, TL,Wang, LZ,et al. BRD4-specific PROTAC inhibits basal-like breast cancer partially through downregulating KLF5 expression[J]. ONCOGENE,2024,43(39):2914-2926.
APA	Kong, YJ.,Lan, TL.,Wang, LZ.,Gong, C.,Lv, WX.,...&Chen, CS.(2024).BRD4-specific PROTAC inhibits basal-like breast cancer partially through downregulating KLF5 expression.ONCOGENE,43(39),2914-2926.
MLA	Kong, YJ,et al."BRD4-specific PROTAC inhibits basal-like breast cancer partially through downregulating KLF5 expression".ONCOGENE 43.39(2024):2914-2926.

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