N-Myc-interacting protein (NMI) negatively regulates epithelial-mesenchymal transition by inhibiting the acetylation of NF-κB/p65
N-Myc-interacting protein (NMI) negatively regulates epithelial-mesenchymal transition by inhibiting the acetylation of NF-κB/p65
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N-Myc 相互作用蛋白 (NMI) 通过抑制 NF-kappa B/p65 的乙酰化来负向调节上皮间质转化
DOI：
10.1016/j.canlet.2016.02.015
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发表时间：
2016-06-28
期刊：
影响因子：
9.7
通讯作者：
Cai, Jian-Chun
中科院分区：
文献类型：
--
作者：
Hou, Jingjing;Wang, Tao;Cai, Jian-Chun
上皮-间质转化（EMT）在胚胎发育、创伤愈合、组织再生、器官纤维化和肿瘤进展中起重要作用。然而，这一过程的机制知之甚少。许多信号传导途径，包括NF-κ B信号传导途径，在发育和分化过程中触发EMT。在本研究中，我们报告了N-Myc相互作用因子（NMI）通过抑制NF-κ B B的转录活性来抑制人胃癌细胞中EMT的进展。我们发现NMI的表达在浸润性胃癌细胞和胃癌组织中显著降低。NMI的过表达抑制细胞的迁移和侵袭，并且这种抑制在TNF-α刺激后增强。裸鼠致瘤性试验支持NMI抑制癌细胞EMT的观点。从机制上讲，NMI促进NF-κ B/p65和组蛋白脱乙酰酶（HDAC）之间的相互作用，并抑制p65的乙酰化和转录活性。p65的表达挽救了匪I介导的EMT抑制，并且由匪I介导的p65乙酰化的抑制是HDAC依赖性的。总之，这些发现表明，NMI可以通过抑制NF-κ B B通路来抑制肿瘤的侵袭和转移，为胃肿瘤中EMT的抑制提供了另一种机制。(C)2016爱思唯尔爱尔兰有限公司版权所有。
The epithelial-mesenchymal transition (EMT) plays an essential role in embryonic development, wound healing, tissue regeneration, organ fibrosis, and tumor progression. However, the mechanisms underlying this process are poorly understood. Many signaling pathways, including the NF-kappa B signaling pathway, trigger EMT during development and differentiation. In the present study, we report that N-Myc interactor (NMI) inhibits EMT progression by suppressing transcriptional activities of NF-kappa B in human gastric cancer cells. We show that the expression of NMI is significantly reduced in invasive gastric cancer cells and gastric cancer tissues. Overexpression of NMI inhibited cell migration and invasion, and this inhibition was enhanced after TNF-alpha stimulation. Tumorigenicity assay in nude mice support the notion that NMI inhibits EMT in cancer cells. Mechanistically, NMI promotes the interaction between NF-kappa B/p65 and histone deacetylases (HDACs) and inhibits the acetylation and transcriptional activity of p65. The expression of p65 rescues NMI-mediated inhibition of EMT and the inhibition of the acetylation of p65 mediated by NMI is HDACs-dependent. Taken together, these findings suggest that NMI can suppress tumor invasion and metastasis by inhibiting NF-kappa B pathways, providing an alternative mechanism for EMT inhibition in stomach neoplasm. (C) 2016 Elsevier Ireland Ltd. All rights reserved.