title: 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.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan 410082, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan 410082, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan 410082, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan 410082, China.
authors.forename: Tuanhui
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan 410082, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Qian
authors.affiliation: Department of Pathology, Hunan Provincial Tumor Hospital, Changsha, Hunan 410013, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan 410082, China. Electronic address: yjtan@hnu.edu.cn.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics* / Q000378:metabolism; D064593:Heterografts; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D015820:Cadherins; C496502:FOXA2 protein, human; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D051542:Hepatocyte Nuclear Factor 3-beta
keywords: Breast cancer; E-cadherin transcription; EMT; FOXA2 transcription factor; ZEB2 transcription