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Cited by 320

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Differential Regulation of Epithelial and Mesenchymal Markers by δEF1 Proteins in Epithelial–Mesenchymal Transition Induced by TGF-β

Open access
Shirakihara, Takuya, Saitoh, Masao, Miyazono, Kohei·2007·Molecular Biology of the Cell

Abstract

Epithelial–mesenchymal transition (EMT), a crucial event in cancer progression and embryonic development, is induced by transforming growth factor (TGF)-β in mouse mammary NMuMG epithelial cells. Id proteins have previously been reported to inhibit major features of TGF-β–induced EMT. In this study, we show that expression of the δEF1 family proteins, δEF1 (ZEB1) and SIP1, is gradually increased by TGF-β with expression profiles reciprocal to that of E-cadherin. SIP1 and δEF1 each dramatically down-regulated the transcription of E-cadherin in NMuMG cells through direct binding to the E-cadherin promoter. Silencing of the expression of both SIP1 and δEF1, but not either alone, completely abolished TGF-β–induced E-cadherin repression. However, expression of mesenchymal markers, including fibronectin, N-cadherin, and vimentin, was not affected by knockdown of SIP1 and δEF1. TGF-β–induced the expression of Ets1, which in turn activated δEF1 promoter activity. Moreover, up-regulation of SIP1 and δEF1 expression by TGF-β was suppressed by knockdown of Ets1 expression. In addition, Id2 suppressed the TGF-β– and Ets1-induced up-regulation of δEF1. Taken together, these findings suggest that the δEF1 family proteins, SIP1 and δEF1, are necessary, but not sufficient, for TGF-β–induced EMT and that Ets1 induced by TGF-β may function as an upstream transcriptional regulator of SIP1 and δEF1.

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Metadata

Authors
Shirakihara, T., Saitoh, M., & Miyazono, K.
Venue
Molecular Biology of the Cell
Published
2007-09
Volume
18
Issue
9
Pages
3533-3544
ISSN
  • 1059-1524 (ISSN-L)
  • 1939-4586
OpenAlex
W2103919722
Cited by
320
References
52
FWCI
6.59
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Differential Regulation of Epithelial and Mesenchymal Markers by δEF1 Proteins in Epithelial–Mesenchymal Transition Induced by TGF-β. https://app.cochat.ai/papers/10.1091/mbc.e07-03-0249
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Shirakihara, T., Saitoh, M., & Miyazono, K. (2007). Differential Regulation of Epithelial and Mesenchymal Markers by δEF1 Proteins in Epithelial–Mesenchymal Transition Induced by TGF-β. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.e07-03-0249

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