NF-kappaB Is Involved in the Regulation of EMT Genes in Breast Cancer Cells.

PloS one

PubMedID: 28107418

Pires BR, Mencalha AL, Ferreira GM, de Souza WF, Morgado-Díaz JA, Maia AM, Corrêa S, Abdelhay ES. NF-kappaB Is Involved in the Regulation of EMT Genes in Breast Cancer Cells. PLoS ONE. 2017;12(1):e0169622.
The metastatic process in breast cancer is related to the expression of the epithelial-to-mesenchymal transition transcription factors (EMT-TFs) SNAIL, SLUG, SIP1 and TWIST1. EMT-TFs and nuclear factor-?B (NF-?B) activation have been associated with aggressiveness and metastatic potential in carcinomas. Here, we sought to examine the role of NF-?B in the aggressive properties and regulation of EMT-TFs in human breast cancer cells. Blocking NF-?B/p65 activity by reducing its transcript and protein levels (through siRNA-strategy and dehydroxymethylepoxyquinomicin [DHMEQ] treatment) in the aggressive MDA-MB-231 and HCC-1954 cell lines resulted in decreased invasiveness and migration, a downregulation of SLUG, SIP1, TWIST1, MMP11 and N-cadherin transcripts and an upregulation of E-cadherin transcripts. No significant changes were observed in the less aggressive cell line MCF-7. Bioinformatics tools identified several NF-?B binding sites along the promoters of SNAIL, SLUG, SIP1 and TWIST1 genes. Through chromatin immunoprecipitation and luciferase reporter assays, the NF-?B/p65 binding on TWIST1, SLUG and SIP1 promoter regions was confirmed. Thus, we suggest that NF-?B directly regulates the transcription of EMT-TF genes in breast cancer. Our findings may contribute to a greater understanding of the metastatic process of this neoplasia and highlight NF-?B as a potential target for breast cancer treatment.