OVOL2 antagonizes TGF-β signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis
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Updated: Mar 3, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Rong-Si Wu1,2, Jing-Jing Hong1,2, Jia-Fa Wu1,3
1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
Abstract:
Great progress has been achieved in the study of the role of TGF-β signaling in triggering epithelial-mesenchymal transition (EMT) in a variety of cancers; however, the regulation of TGF-β signaling during EMT in mammary tumor metastasis has not been completely defined. In the present study, we demonstrated that OVOL2, a zinc finger transcription factor, inhibits TGF-β signaling-induced EMT in mouse and human mammary tumor cells, as well as in mouse tumor models. Data from the Oncomine databases indicated a strong negative relationship between OVOL2 expression and breast cancer progression. Moreover, our experiments revealed that OVOL2 inhibits TGF-β signaling at multiple levels, including inhibiting Smad4 mRNA expression and inducing Smad7 mRNA expression, blocking the binding between Smad4 and target DNA, and interfering with complex formation between Smad4 and Smad2/3. These findings reveal a novel mechanism that controls the TGF-β signaling output level in vitro and in vivo. The modulation of these molecular processes may represent a strategy for inhibiting breast cancer invasion by restoring OVOL2 expression.
Insights
OVOL2, a transcription factor, inhibits epithelial-mesenchymal transition (EMT) in breast cancer by suppressing TGF-β signaling. Restoring OVOL2 may offer a strategy to reduce mammary tumor invasion and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Transforming growth factor-beta (TGF-β) signaling drives epithelial-mesenchymal transition (EMT), crucial for cancer metastasis.
- The precise regulation of TGF-β signaling during mammary tumor metastasis remains incompletely understood.
Purpose of the Study:
- To investigate the role of OVOL2 in regulating TGF-β signaling-induced EMT in breast cancer.
- To elucidate the molecular mechanisms by which OVOL2 influences TGF-β signaling pathways.
Main Methods:
- Utilized mouse and human mammary tumor cells and mouse tumor models.
- Analyzed OVOL2 expression in relation to breast cancer progression using Oncomine databases.
- Performed molecular experiments to assess OVOL2's impact on TGF-β signaling components (Smad4, Smad7, Smad2/3).
Main Results:
- OVOL2 significantly inhibits TGF-β signaling-induced EMT in mammary tumor cells and models.
- OVOL2 expression negatively correlates with breast cancer progression.
- OVOL2 interferes with TGF-β signaling by modulating Smad4 and Smad7 mRNA levels and disrupting Smad complex formation and DNA binding.
Conclusions:
- OVOL2 acts as a novel inhibitor of TGF-β signaling, controlling its output at multiple molecular levels.
- Restoring OVOL2 expression presents a potential therapeutic strategy to inhibit breast cancer invasion and metastasis.
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