N-Myc-interacting protein (NMI) negatively regulates epithelial-mesenchymal transition by inhibiting the acetylation of NF-κB/p65
Author links open overlay panelJingjingHouabcTaoWangabcQingqingXiedWeixianDengabJames Y.YangdSi QingZhangdJian-ChunCaiabc
aDepartment of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, ChinabInstitute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, Fujian, 361004, ChinacXiehe Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, 350001, ChinadState Key Laboratory of Cellular Stress Biology and School of Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China
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
NMIEMTNF-κBHDACsstomach neoplasm