FOXF2 deficiency promotes epithelial-mesenchymal transition and metastasis of basal-like breast cancer

Breast Cancer Res. 2015 Feb 26;17(1):30. doi: 10.1186/s13058-015-0531-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma, Basal Cell / genetics*
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Forkhead Transcription Factors / deficiency*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Nuclear Proteins / genetics
  • Phenotype
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Messenger / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Twist-Related Protein 1 / genetics


  • FOXF2 protein, human
  • Forkhead Transcription Factors
  • Nuclear Proteins
  • RNA, Messenger
  • TWIST1 protein, human
  • Transcription Factors
  • Twist-Related Protein 1