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Updated: Feb 4, 2026
Induction of Mesenchymal-Epithelial Transitions in Sarcoma Cells
Published on: April 7, 2017
Foxf2 plays a dual role during transforming growth factor beta-induced epithelial to mesenchymal transition by
Nathalie Meyer-Schaller1,2, Chantal Heck1,3, Stefanie Tiede1
1Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland.
Background:
The most life-threatening step during malignant tumor progression is reached when cancer cells leave the primary tumor mass and seed metastasis in distant organs. To infiltrate the surrounding tissue and disseminate throughout the body, single motile tumor cells leave the tumor mass by breaking down cell-cell contacts in a process called epithelial to mesenchymal transition (EMT). An EMT is a complex molecular and cellular program enabling epithelial cells to abandon their differentiated phenotype, including cell-cell adhesion and cell polarity, and to acquire mesenchymal features and invasive properties.
Methods:
We employed gene expression profiling and functional experiments to study transcriptional control of transforming growth factor (TGF)β-induced EMT in normal murine mammary gland epithelial (NMuMG) cells.
Results:
We identified that expression of the transcription factor forkhead box protein F2 (Foxf2) is upregulated during the EMT process. Although it is not required to gain mesenchymal markers, Foxf2 is essential for the disruption of cell junctions and the downregulation of epithelial markers in NMuMG cells treated with TGFβ. Foxf2 is critical for the downregulation of E-cadherin by promoting the expression of the transcriptional repressors of E-cadherin, Zeb1 and Zeb2, while repressing expression of the epithelial maintenance factor Id2 and miRNA 200 family members. Moreover, Foxf2 is required for TGFβ-mediated apoptosis during EMT by the transcriptional activation of the proapoptotic BH3-only protein Noxa and by the negative regulation of epidermal growth factor receptor (EGFR)-mediated survival signaling through direct repression of its ligands betacellulin and amphiregulin. The dual function of Foxf2 during EMT is underscored by the finding that high Foxf2 expression correlates with good prognosis in patients with early noninvasive stages of breast cancer, but with poor prognosis in advanced breast cancer.
Conclusions:
Our data identify the transcription factor Foxf2 as one of the important regulators of EMT, displaying a dual function in promoting tumor cell apoptosis as well as tumor cell migration.
Insights
Forkhead box protein F2 (Foxf2) drives epithelial to mesenchymal transition (EMT) by disrupting cell junctions and promoting apoptosis. Its role in cancer progression shows a dual prognostic significance in breast cancer patients.
Area of Science:
- Molecular biology
- Cancer research
- Cellular biology
Background:
- Malignant tumor progression involves cancer cells detaching from the primary tumor and metastasizing.
- Epithelial to mesenchymal transition (EMT) is a key process enabling cancer cells to gain motility and invasiveness.
- EMT involves loss of epithelial characteristics and acquisition of mesenchymal features.
Purpose of the Study:
- To investigate the transcriptional control of transforming growth factor (TGF)β-induced EMT.
- To identify key regulators of EMT in normal murine mammary gland epithelial (NMuMG) cells.
Main Methods:
- Gene expression profiling
- Functional experiments
- Analysis of TGFβ-induced EMT in NMuMG cells
Main Results:
- Forkhead box protein F2 (Foxf2) expression is upregulated during EMT.
- Foxf2 is essential for disrupting cell junctions and downregulating epithelial markers.
- Foxf2 promotes apoptosis and suppresses EGFR-mediated survival signaling during EMT.
- Foxf2 expression correlates with prognosis in breast cancer patients, with dual implications based on stage.
Conclusions:
- Foxf2 is a critical regulator of EMT with a dual role.
- Foxf2 promotes both tumor cell apoptosis and migration.
- Understanding Foxf2's function is crucial for therapeutic strategies in breast cancer.
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