Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers

Sendurai A. Mani, Jing Yang, Mary Brooks, Gunda Schwaninger, Alicia Zhou, Naoyuki Miura, Jeffery L. Kutok, Kimberly Hartwell, Andrea L. Richardson, Robert A. Weinberg

Research output: Contribution to journalArticlepeer-review


The metastatic spread of epithelial cancer cells from the primary tumor to distant organs mimics the cell migrations that occur during embryogenesis. Using gene expression profiling, we have found that the FOXC2 transcription factor, which is involved in specifying mesenchymal cell fate during embryogenesis, is associated with the metastatic capabilities of cancer cells. FOXC2 expression is required for the ability of murine mammary carcinoma cells to metastasize to the lung, and overexpression of FOXC2 enhances the metastatic ability of mouse mammary carcinoma cells. We show that FOXC2 expression is induced in cells undergoing epithelial-mesenchymal transitions (EMTs) triggered by a number of signals, including TGF-β1 and several EMT-inducing transcription factors, such as Snail, Twist and Goosecoid. FOXC2 specifically promotes mesenchymal differentiation during an EMT and may serve as a key mediator to orchestrate the mesenchymal component of the EMT program. Expression of FOXC2 is significantly correlated with the highly aggressive basal-like subtype of human breast cancers. These observations indicate that FOXC2 plays a central role in promoting invasion and metastasis and that it may prove to be a highly specific molecular marker for human basal-like breast cancers.

Original languageEnglish (US)
Pages (from-to)10069-10074
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - Jun 12 2007
Externally publishedYes


  • Embryogenesis
  • Epithelial-mesenchymal transition
  • Twist and snail

ASJC Scopus subject areas

  • General


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