Transcriptional factors p300 and MRTF-A synergistically enhance the expression of migration-related genes in MCF-7 breast cancer cells
Transcriptional factors p300 and MRTF-A synergistically enhance the expression of migration-related genes in MCF-7 breast cancer cells
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转录因子p300和MRTF-A协同增强MCF-7乳腺癌细胞迁移相关基因的表达
DOI：
10.1016/j.bbrc.2015.10.060
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发表时间：
2015-11-27
影响因子：
3.1
通讯作者：
Zhang, Tong-Cun
中科院分区：
文献类型：
--
作者：
He, Hongpeng;Wang, Dandan;Zhang, Tong-Cun
转录辅激活因子p300在乳腺癌组织中高度表达。MRTF-A是一种受Rho-GTdR-actin信号通路控制的转录因子。本研究旨在探讨p300在乳腺癌转移中的作用。我们发现p300的过表达增强了乳腺癌细胞的运动能力，同时也上调了与运动相关的基因的转录。p300的缺失下调了迁移相关基因，减缓了乳腺癌细胞的迁移。p300与MRTF-A协同作用以激活MYH 9、MYL 9和CYR 61的转录。如co-IP所鉴定的，p300与MRTF-A的C-末端结构域相互作用。p300与MRTF-A一起与靶基因启动子相关。此外，发现MRTF-A在MCF-7乳腺癌细胞中被乙酰化。这些结果表明p300参与了MRTF-A介导的基因调控和乳腺癌细胞迁移。(C)2015 Elsevier Inc. All rights reserved.
The transcriptional coactivator p300 is highly expressed in breast cancer tissues. MRTF-A is a transcription factor governed by the Rho-GTPase-actin signaling pathway. The purpose of this study was to explore the role of p300 in breast cancer metastasis. Here we showed that the motility of breast cancer cells was enhanced by the overexpression of p300, meanwhile, the transcription of migration-related genes was upregulated. Depletion of p300 downregulated the migration-related genes and slowed down the migration of breast cancer cells. p300 worked synergistically with MRTF-A to activate the transcription of MYH9, MYL9 and CYR61. As identified by co-IP, p300 interacted with the C-terminal TAD domain of MRTF-A. And together with MRTF-A, p300 was associated with the target gene promoters. Furthermore, MRTF-A was found to be acetylated in MCF-7 breast cancer cells. These results demonstrated the involvement of p300 in the MRTF-A mediated gene regulation and breast cancer cell migration. (C) 2015 Elsevier Inc. All rights reserved.