Identification of EGF-NF-κB-FOXC1 signaling axis in basal-like breast cancer

The 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 fa...

Full description

Saved in:
Bibliographic Details
Published in:Cell communication and signaling 2017-06, Vol.15 (1), p.22-22, Article 22
Main Authors: Chung, Stacey, Jin, Yanli, Han, Bingchen, Qu, Ying, Gao, Bowen, Giuliano, Armando E, Cui, Xiaojiang
Format: Article
Language:English
Subjects:
Basal-like breast cancer
Base Sequence
Breast Neoplasms - pathology
Cell Line, Tumor
Epidermal growth factor
Epidermal Growth Factor - metabolism
Forkhead Transcription Factors - genetics
Forkhead Transcription Factors - metabolism
FOXC1
Humans
NF-kappa B - metabolism
NF-κB
Promoter Regions, Genetic - genetics
Short Report
Signal Transduction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The 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. Luciferase 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. In 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. Collectively, 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.
ISSN:1478-811X
1478-811X
DOI:10.1186/s12964-017-0180-3