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Cell Communication and Signaling

, 15:22

First Online: 19 June 2017Received: 03 December 2016Accepted: 14 June 2017DOI: 10.1186-s12964-017-0180-3

Cite this article as: Chung, S., Jin, Y., Han, B. et al. Cell Commun Signal 2017 15: 22. doi:10.1186-s12964-017-0180-3


BackgroundThe pathogenesis of human basal-like breast cancer BLBC is not well understood and patients with BLBC have a poor prognosis. Expression of the epidermal growth factor receptor EGFR and nuclear factor-κB NF-κB is well-known to be upregulated in BLBC. The forkhead box C1 FOXC1 transcription factor, an important prognostic biomarker specific for BLBC, has been shown to be induced by EGF and is critical for EGF effects in breast cancer cells. How FOXC1 is transcriptionally activated in BLBC is not clear.

MethodsLuciferase reporter assays were performed to show that NF-κB-p65 enhances FOXC1 promoter activity in BLBC cells MDA-MB-468. Electrophoretic mobility shift assay, biotinylated oligonucleotide precipitation assay, and chromatin immunoprecipitation assay were used to show that NF-κB interacts and binds to the promoter region of FOXC1.

ResultsIn this study, we demonstrate that NF-κB is a pivotal mediator of the EGF-EGFR regulation of FOXC1 expression by binding to the FOXC1 promoter to activate FOXC1 transcription. Loss or inhibition of NF-κB diminished FOXC1 expression.

ConclusionCollectively, our findings reveal a novel EGFR-NF-κB-FOXC1 signaling axis that is critical for BLBC cell function, supporting the notion that intervention in the FOXC1 pathway may provide potential modalities for BLBC treatment.

KeywordsFOXC1 Epidermal growth factor NF-κB Basal-like breast cancer AbbreviationsBLBCBasal-like breast cancer

ChIPChromatin immunoprecipitation


EGFEpidermal growth factor

EGFREpidermal growth factor receptor

EMSAElectrophoretic mobility shift assay

EREstrogen receptor

FOXC1Forkhead box C1

HER2Human epidermal growth factor receptor 2

IKKIκB kinase

MEFsMouse embryonic fibroblasts

NF-κBNuclear factor-κB

PRProgesterone receptor

siRNAsmall interfering RNA

SR-IκBαIκBα S32A-S36A super-repressor

Electronic supplementary materialThe online version of this article doi:10.1186-s12964-017-0180-3 contains supplementary material, which is available to authorized users.

Autor: Stacey Chung - Yanli Jin - Bingchen Han - Ying Qu - Bowen Gao - Armando E. Giuliano - Xiaojiang Cui


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