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01-12-2014 | Translational Research and Biomarkers

FOXC1 is a Critical Mediator of EGFR Function in Human Basal-like Breast Cancer

Authors: Yanli Jin, PhD, Bingchen Han, PhD, Jiongyu Chen, BS, Ruprecht Wiedemeyer, PhD, Sandra Orsulic, PhD, Shikha Bose, MD, Xiao Zhang, PhD, Beth Y. Karlan, MD, Armando E. Giuliano, MD, Yukun Cui, PhD, Xiaojiang Cui, PhD

Published in: Annals of Surgical Oncology | Special Issue 4/2014

Abstract

Background

Human basal-like breast cancer (BLBC) has a poor prognosis and is often identified by expression of the epidermal growth factor receptor (EGFR). BLBC remains a major clinical challenge because its pathogenesis is not well understood, thus hindering efforts to develop targeted therapies. Recent data implicate the forkhead box C1 (FOXC1) transcription factor as an important prognostic biomarker and functional regulator of BLBC, but its regulatory mechanism and impact on BLBC tumorigenesis remain unclear.

Methods

The association between FOXC1 and EGFR expression in human breast cancer was examined by immunohistochemistry in formalin-fixed tissues and analysis of the TCGA database. The regulation of FOXC1 by EGFR activation was investigated in MDA-MB-468 cells using immunoblotting, qRT-PCR, and luciferase activity assays. This EGFR effect on FOXC1 expression was confirmed using the MDA-MB-468 xenograft model.

Results

Both FOXC1 mRNA and protein levels significantly correlated with EGFR expression in human breast tumors. EGFR activation induced FOXC1 transcription through the ERK and Akt pathways in BLBC. EGFR inhibition in vivo reduced FOXC1 expression in xenograft tumors. We also found that FOXC1 knockdown impaired the effects of EGF on BLBC cell proliferation, migration, and invasion.

Conclusions

Our findings uncover a novel EGFR-FOXC1 signaling axis critical for BLBC cell functions, supporting the notion that intervention in the FOXC1 pathway may provide potential modalities for BLBC treatment.

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Title: FOXC1 is a Critical Mediator of EGFR Function in Human Basal-like Breast Cancer
Authors: Yanli Jin, PhD
Bingchen Han, PhD
Jiongyu Chen, BS
Ruprecht Wiedemeyer, PhD
Sandra Orsulic, PhD
Shikha Bose, MD
Xiao Zhang, PhD
Beth Y. Karlan, MD
Armando E. Giuliano, MD
Yukun Cui, PhD
Xiaojiang Cui, PhD
Publication date: 01-12-2014
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue Special Issue 4/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-014-3980-3

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

FOXC1 is a Critical Mediator of EGFR Function in Human Basal-like Breast Cancer

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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