title: NF-kappaB Is Involved in the Regulation of EMT Genes in Breast Cancer Cells.
abstract: 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.
authors.affiliation: Laboratório de Célula-Tronco, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Ciência e Tecnologia para o Controle do Câncer, Rio de Janeiro, RJ, Brazil.
authors.forename: Bruno R B
authors.identifier: http://orcid.org/0000-0002-0429-7871
authors.initials: BR
authors.lastname: Pires
authors.affiliation: Departamento de Biofísica e Biometria, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Andre L
authors.initials: AL
authors.lastname: Mencalha
authors.affiliation: Laboratório de Célula-Tronco, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Ciência e Tecnologia para o Controle do Câncer, Rio de Janeiro, RJ, Brazil.
authors.forename: Gerson M
authors.initials: GM
authors.lastname: Ferreira
authors.affiliation: Grupo de Biologia Estrutural, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, RJ, Brazil.
authors.forename: Waldemir F
authors.initials: WF
authors.lastname: de Souza
authors.affiliation: Grupo de Biologia Estrutural, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, RJ, Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Morgado-Díaz
authors.affiliation: Laboratório de Célula-Tronco, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Ciência e Tecnologia para o Controle do Câncer, Rio de Janeiro, RJ, Brazil.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Maia
authors.affiliation: Laboratório de Célula-Tronco, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Ciência e Tecnologia para o Controle do Câncer, Rio de Janeiro, RJ, Brazil.
authors.forename: Stephany
authors.initials: S
authors.lastname: Corrêa
authors.affiliation: Laboratório de Célula-Tronco, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, RJ, Brazil.|Instituto Nacional de Ciência e Tecnologia para o Controle do Câncer, Rio de Janeiro, RJ, Brazil.
authors.forename: Eliana S F W
authors.initials: ES
authors.lastname: Abdelhay
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics
chemical_list: D016328:NF-kappa B; D014157:Transcription Factors