OVOL2 antagonizes TGF-β signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis
| Autor: | Zhi-Ming Zhang, Yuan-Yuan Xie, Shen Yan, Na Liu, Err-Cheng Chan, Yun-Jia Liu, Jia-Fa Wu, Jing-Jing Hong, Rong-Si Wu, Di Wu, Bo-An Li, Qiu-Wan Wu, Zhong-Zheng Zheng, Qing-Feng Liu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Breast Neoplasms Kaplan-Meier Estimate TGF-β signaling Smad7 Protein Metastasis Mice 03 medical and health sciences Breast cancer Cell Movement Transforming Growth Factor beta In vivo Cell Line Tumor medicine Animals Humans Epithelial–mesenchymal transition Neoplasm Metastasis Cell Proliferation Smad4 Protein Zinc finger transcription factor Mammary tumor business.industry Tumor Suppressor Proteins EMT OVOL2 Prognosis medicine.disease mammary tumor In vitro DNA-Binding Proteins Disease Models Animal 030104 developmental biology Oncology Immunology Cancer research Female Smad4 business Biomarkers Research Paper Protein Binding Signal Transduction Transcription Factors Transforming growth factor |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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