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

SA Mani, J Yang, M Brooks… - Proceedings of the …, 2007 - National Acad Sciences
SA Mani, J Yang, M Brooks, G Schwaninger, A Zhou, N Miura, JL Kutok, K Hartwell…
Proceedings of the National Academy of Sciences, 2007National Acad Sciences
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 …
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.
National Acad Sciences