FOXA2 attenuates the epithelial to mesenchymal transition by regulating the transcription of E-cadherin and ZEB2 in human breast cancer.

Abstract

The Forkhead Box A2 (FOXA2) transcription factor is required for embryonic development and for normal functions of multiple adult tissues, in which the maintained expression of FOXA2 is usually related to preventing the progression of malignant transformation. In this study, we found that FOXA2 prevented the epithelial to mesenchymal transition (EMT) in human breast cancer. We observed a strong correlation between the expression levels of FOXA2 and the epithelial phenotype. Knockdown of FOXA2 promoted the mesenchymal phenotype, whereas stable overexpression of FOXA2 attenuated EMT in breast cancer cells. FOXA2 was found to endogenously bind to and stimulate the promoter of E-cadherin that is crucial for epithelial phenotype of the tumor cells. Meanwhile, FOXA2 prevented EMT of breast cancer cells by repressing the expression of EMT-related transcription factor ZEB2 through recruiting a transcriptional corepressor TLE3 to the ZEB2 promoter. The stable overexpression of FOXA2 abolished metastasis of breast cancer cells in vivo. This study confirmed that FOXA2 inhibited EMT in breast cancer cells by regulating the transcription of EMT-related genes such as E-cadherin and ZEB2.

• Authors: Zhen Zhang, Chao Yang, Wei Gao, Tuanhui Chen, Tingting Qian, Jun Hu, Yongjun Tan
• Journal: Cancer letters (Cancer Lett) Vol. 361 Issue 2 Pg. 240-50 (Jun 01 2015) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 25779673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Cadherins
• FOXA2 protein, human
• Homeodomain Proteins
• Repressor Proteins
• ZEB2 protein, human
• Zinc Finger E-box Binding Homeobox 2
• Hepatocyte Nuclear Factor 3-beta

Topics

• Animals
• Breast Neoplasms (genetics, pathology)
• Cadherins (genetics, metabolism)
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• HEK293 Cells
• Hepatocyte Nuclear Factor 3-beta (genetics, metabolism)
• Heterografts
• Homeodomain Proteins (genetics, metabolism)
• Humans
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Repressor Proteins (genetics, metabolism)
• Transcription, Genetic
• Transfection
• Zinc Finger E-box Binding Homeobox 2