Journal Article

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

Morgado-Díaz, José A., Pires, Bruno R. B., Abdelhay, Eliana S. F. W., Maia, Amanda M., de Souza, Waldemir F., Corrêa, Stephany, Mencalha, Andre L., Ferreira, Gerson M.

2017

Overview

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-κB (NF-κB) activation have been associated with aggressiveness and metastatic potential in carcinomas. Here, we sought to examine the role of NF-κB in the aggressive properties and regulation of EMT-TFs in human breast cancer cells. Blocking NF-κB/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-κB binding sites along the promoters of SNAIL, SLUG, SIP1 and TWIST1 genes. Through chromatin immunoprecipitation and luciferase reporter assays, the NF-κB/p65 binding on TWIST1, SLUG and SIP1 promoter regions was confirmed. Thus, we suggest that NF-κB 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-κB as a potential target for breast cancer treatment.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Binding sites / Bioinformatics / Biology and Life Sciences / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - pathology / Cancer / Cancer cells / Carcinoma / Cell adhesion & migration / Cell cycle / Cell Line, Tumor / Chromatin / Chromatin Immunoprecipitation / E-cadherin / Epithelial-Mesenchymal Transition - genetics / Gene expression / Gene Expression Regulation, Neoplastic / Gene regulation / Genes / Genetic aspects / Genetic regulation / Genotype & phenotype / Humans / Immunoprecipitation / Invasiveness / Kinases / Medicine and Health Sciences / Mesenchyme / Metastases / Metastasis / N-Cadherin / NF-kappa B - metabolism / NF-κB protein / Physiological aspects / Promoter Regions, Genetic / Prostate cancer / Research and Analysis Methods / Rodents / siRNA / Snail protein / Transcription factors / Transcription Factors - genetics / Tumors