NFAT1 Hypermethylation Promotes Epithelial-Mesenchymal Transition and Metastasis in Nasopharyngeal Carcinoma by Activating ITGA6 Transcription

• Published in: Neoplasia (New York, N.Y.) Vol. 21; no. 3; pp. 311 - 321
• Main Authors: Zhang, Jian, Zheng, Zi-Qi, Yuan, Ya-Wei, Zhang, Pan-Pan, Li, Ying-Qin, Wang, Ya-Qin, Tang, Xin-Ran, Wen, Xin, Hong, Xiao-Hong, Lei, Yuan, He, Qing-Mei, Yang, Xiao-Jing, Sun, Ying, Ma, Jun, Liu, Na
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2019; Elsevier Limited; Elsevier
• Subjects: Carcinogenesis; Cell adhesion & migration; Cell Line, Tumor; Cell migration; DNA Methylation; DNA microarrays; Epigenesis, Genetic; Epithelial-Mesenchymal Transition - genetics; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genomes; Humans; Integrin alpha6 - genetics; Lymphatic Metastasis; Mesenchyme; Metastases; Metastasis; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - genetics; Nasopharyngeal Carcinoma - pathology; Neoplasm Staging; NF-AT1 protein; NFATC Transcription Factors - genetics; RNA Interference; Transcriptional Activation; Transcriptome; Tumor suppressor genes
• ISSN: 1476-5586; 1522-8002; 1476-5586
• DOI: 10.1016/j.neo.2019.01.006

DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1/ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy.