OVOL2 antagonizes TGF-β signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis

Rong Si Wu, Jing Jing Hong, Jia Fa Wu, Shen Yan, Di Wu, Na Liu, Qing Feng Liu, Qiu Wan Wu, Yuan Yuan Xie, Yun Jia Liu, Zhong Zheng Zheng, Err Cheng Chan, Zhi Ming Zhang, Bo An Li*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

32 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)39401-39416
頁數16
期刊Oncotarget
8
發行號24
DOIs
出版狀態已出版 - 2017

文獻附註

Publisher Copyright:
© Wu et al.

指紋

深入研究「OVOL2 antagonizes TGF-β signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis」主題。共同形成了獨特的指紋。

引用此