Histone deacetylase 8 triggers the migration of triple negative breast cancer cells via regulation of YAP signals

被引:28
作者
An, Panpan [1 ]
Li, Jiexin [1 ]
Lu, Linlin [1 ]
Wu, Yingmin [1 ]
Ling, Yuyi [1 ]
Du, Jun [1 ]
Chen, Zhuojia [2 ]
Wang, Hongsheng [1 ]
机构
[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Dept Microbial & Biochem Pharm, Guangdong Prov Key Lab New Drug Design & Evaluat, Guangzhou 510006, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
TNBC; Migration; HDAC8; YAP; TRANSCRIPTION; HDAC8; PROTEIN;
D O I
10.1016/j.ejphar.2018.12.030
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Triple-negative breast cancer (TNBC) shows highly aggressive clinical behaviors and poor prognosis compared to other breast cancer subtypes. Histone deacetylases (HDACs) can regulate the progression of various cancers, but the role of HDAC8 in TNBC remains unexplored. Here, we found that HDAC8 enhanced the in vitro migration abilities of breast cancer cells. Targeted inhibition of HDAC8 via si-HDAC8 and its selective inhibitor PCI34051 could suppress the migration of cells. In TNBC cells, HDAC8 stabilized the expression and increased the nuclear localization of YAP, a major downstream effector of Hippo pathway. While silencing YAP could attenuate HDAC8 triggered migration of TNBC cells. Mechanistically, HDAC8 suppressed the phosphorylation of YAP(ser127), which was related to its cytoplasmic sequestration degradation. Our data revealed that HDAC8 could trigger the migration of TNBC cells via regulation of Hippo-YAP signals, suggesting that HDAC8 might be a potential target for TNBC therapy.
引用
收藏
页码:16 / 23
页数:8
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