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

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 carcino...

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Bibliographic Details
Published in:PloS one 2017-01, Vol.12 (1), p.e0169622-e0169622
Main Authors: Pires, Bruno R B, Mencalha, Andre L, Ferreira, Gerson M, de Souza, Waldemir F, Morgado-Díaz, José A, Maia, Amanda M, Corrêa, Stephany, Abdelhay, Eliana S F W
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0169622