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Cancer Lett. 2016 Jun 28;376(1):22-33. doi: 10.1016/j.canlet.2016.02.015. Epub 2016 Mar 21.

N-Myc-interacting protein (NMI) negatively regulates epithelial-mesenchymal transition by inhibiting the acetylation of NF-κB/p65.

Author information

1
Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, 361004, China; Xiehe Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, 350001, China.
2
State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China.
3
Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, 361004, China.
4
State Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China. Electronic address: zhangsq@xmu.edu.cn.
5
Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, 361004, China; Xiehe Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, 350001, China. Electronic address: jianchunfh2@sina.com.

Abstract

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-κB 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-κB 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-α stimulation. Tumorigenicity assay in nude mice support the notion that NMI inhibits EMT in cancer cells. Mechanistically, NMI promotes the interaction between NF-κB/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-κB pathways, providing an alternative mechanism for EMT inhibition in stomach neoplasm.

KEYWORDS:

EMT; HDACs; NF-κB; NMI; stomach neoplasm

PMID:
27012186
DOI:
10.1016/j.canlet.2016.02.015
[Indexed for MEDLINE]

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