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FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer
INTRODUCTION: Our previous clinical study demonstrated that the under-expression of FOXF2 is associated with early-onset metastasis and poor prognosis of patients with triple-negative breast cancer. In this study, we further characterized the role of FOXF2 in metastasis of basal-like breast cancer (...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361145/ https://www.ncbi.nlm.nih.gov/pubmed/25848863 http://dx.doi.org/10.1186/s13058-015-0531-1 |
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author | Wang, Qing-Shan Kong, Peng-Zhou Li, Xiao-Qing Yang, Fan Feng, Yu-Mei |
author_facet | Wang, Qing-Shan Kong, Peng-Zhou Li, Xiao-Qing Yang, Fan Feng, Yu-Mei |
author_sort | Wang, Qing-Shan |
collection | PubMed |
description | INTRODUCTION: Our previous clinical study demonstrated that the under-expression of FOXF2 is associated with early-onset metastasis and poor prognosis of patients with triple-negative breast cancer. In this study, we further characterized the role of FOXF2 in metastasis of basal-like breast cancer (BLBC) and underlying molecular mechanisms. METHODS: RT-qPCR, immunoblot, immunofluorescence and immunohistochemistry were performed to assess the expression of genes and proteins in cell lines and tissues. A series of in vitro and in vivo assays was performed in the cells with RNAi-mediated knockdown or overexpression to elucidate the function and transcriptional regulatory role of FOXF2 in breast cancer. RESULTS: We found that FOXF2 was specifically expressed in most basal-like breast cells. FOXF2 deficiency enhanced the metastatic ability of BLBC cells in vitro and in vivo. Additionally, FOXF2 deficiency induced the epithelial-mesenchymal transition (EMT) of basal-like breast cells. Furthermore, we identified that TWIST1 is a transcriptional target of FOXF2. TWIST1 was negatively regulated by FOXF2 and mediated the FOXF2-regulated EMT phenotype of basal-like breast cells and aggressive property of BLBC. CONCLUSIONS: FOXF2 is a novel EMT-suppressing transcription factor in BLBC. FOXF2 deficiency enhances metastatic ability of BLBC cells by activating the EMT program through upregulating the transcription of TWIST1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0531-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4361145 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43611452015-03-17 FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer Wang, Qing-Shan Kong, Peng-Zhou Li, Xiao-Qing Yang, Fan Feng, Yu-Mei Breast Cancer Res Research Article INTRODUCTION: Our previous clinical study demonstrated that the under-expression of FOXF2 is associated with early-onset metastasis and poor prognosis of patients with triple-negative breast cancer. In this study, we further characterized the role of FOXF2 in metastasis of basal-like breast cancer (BLBC) and underlying molecular mechanisms. METHODS: RT-qPCR, immunoblot, immunofluorescence and immunohistochemistry were performed to assess the expression of genes and proteins in cell lines and tissues. A series of in vitro and in vivo assays was performed in the cells with RNAi-mediated knockdown or overexpression to elucidate the function and transcriptional regulatory role of FOXF2 in breast cancer. RESULTS: We found that FOXF2 was specifically expressed in most basal-like breast cells. FOXF2 deficiency enhanced the metastatic ability of BLBC cells in vitro and in vivo. Additionally, FOXF2 deficiency induced the epithelial-mesenchymal transition (EMT) of basal-like breast cells. Furthermore, we identified that TWIST1 is a transcriptional target of FOXF2. TWIST1 was negatively regulated by FOXF2 and mediated the FOXF2-regulated EMT phenotype of basal-like breast cells and aggressive property of BLBC. CONCLUSIONS: FOXF2 is a novel EMT-suppressing transcription factor in BLBC. FOXF2 deficiency enhances metastatic ability of BLBC cells by activating the EMT program through upregulating the transcription of TWIST1. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0531-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-02-26 2015 /pmc/articles/PMC4361145/ /pubmed/25848863 http://dx.doi.org/10.1186/s13058-015-0531-1 Text en © Wang et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Wang, Qing-Shan Kong, Peng-Zhou Li, Xiao-Qing Yang, Fan Feng, Yu-Mei FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer |
title | FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer |
title_full | FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer |
title_fullStr | FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer |
title_full_unstemmed | FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer |
title_short | FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer |
title_sort | foxf2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4361145/ https://www.ncbi.nlm.nih.gov/pubmed/25848863 http://dx.doi.org/10.1186/s13058-015-0531-1 |
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