Histone deacetylase 8 triggers the migration of triple negative breast cancer cells via regulation of YAP signals
Histone deacetylase 8 triggers the migration of triple negative breast cancer cells via regulation of YAP signals
复制标题
组蛋白脱乙酰酶 8 通过调节 YAP 信号触发三阴性乳腺癌细胞的迁移
DOI：
10.1016/j.ejphar.2018.12.030
复制
发表时间：
2019-02-15
影响因子：
5
通讯作者：
Wang, Hongsheng
中科院分区：
文献类型：
--
作者：
An, Panpan;Li, Jiexin;Wang, Hongsheng
与其他乳腺癌亚型相比，三阴性乳腺癌(TNBC)表现出高度侵袭性和较差的预后。组蛋白脱乙酰酶(HDACs)可以调节多种癌症的进展，但HDAC8在TNBC中的作用尚不清楚。在这里，我们发现HDAC8增强了乳腺癌细胞的体外迁移能力。通过si-HDAC8及其选择性抑制剂PCI34051靶向抑制HDAC8可以抑制细胞的迁移。在TNBC细胞中，HDAC8稳定了YAP的表达，并增加了YAP的核定位，YAP是河马途径的主要下游效应因子。沉默YAP可减弱HDAC8诱导的TNBC细胞迁移。从机制上讲，HDAC8抑制YAP(Ser127)的磷酸化，这与其胞质隔离降解有关。我们的数据显示，HDAC8可以通过调节Hippo-Yap信号来触发TNBC细胞的迁移，这表明HDAC8可能是TNBC治疗的潜在靶点。
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.