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. 2017;40(9):1483-1489.
doi: 10.1248/bpb.b17-00307.

FOXA1 Induces E-Cadherin Expression at the Protein Level via Suppression of Slug in Epithelial Breast Cancer Cells

Erina Anzai  1 , Kensuke Hirata  1 , Misato Shibazaki  1 , Chiaki Yamada  1 , Mariko Morii  1 , Takuya Honda  1 , Naoto Yamaguchi  1 , Noritaka Yamaguchi  1
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Free article

FOXA1 Induces E-Cadherin Expression at the Protein Level via Suppression of Slug in Epithelial Breast Cancer Cells

Erina Anzai et al. Biol Pharm Bull. 2017.
Free article

Abstract

Epithelial-to-mesenchymal transition (EMT) is an important process during embryonic development and tumor progression by which adherent epithelial cells acquire mesenchymal properties. Forkhead box protein A1 (FOXA1) is a transcriptional regulator preferentially expressed in epithelial breast cancer cells, and its expression is lost in mesenchymal breast cancer cells. However, the implication of this biased expression of FOXA1 in breast cancer is not fully understood. In this study, we analyzed the involvement of FOXA1 in EMT progression in breast cancer, and found that stable expression of FOXA1 in the mesenchymal breast cancer MDA-MB-231 cells strongly induced the epithelial marker E-cadherin at the mRNA and protein levels. Furthermore, stable expression of FOXA1 was found to reduce the mRNA and protein expression of Slug, a repressor of E-cadherin expression. FOXA1 knockdown in the epithelial breast cancer MCF7 cells reduced E-cadherin protein expression without decreasing its mRNA expression. In addition, FOXA1 knockdown in MCF7 cells up-regulated Slug mRNA and protein expression. Notably, similar to FOXA1 knockdown, stable expression of Slug in MCF7 cells reduced E-cadherin protein expression without decreasing its mRNA expression. Taken together, these results suggest that although FOXA1 can induce E-cadherin mRNA expression, it preferentially promotes E-cadherin expression at the protein level by suppressing Slug expression in epithelial breast cancer, and that the balance of this FOXA1-Slug axis regulates EMT progression.

Keywords: E-cadherin; Slug; epithelial–mesenchymal transition; estrogen receptor; forkhead box protein A1.

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