2007 Fiscal Year Final Research Report Summary
Molecular analyses of TGF-β-induced Epithelial-Mesenchymal Transition in oral cancer cells
| Project/Area Number |
18390496
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SAITOH Masao The University of Tokyo, 大学院・医学系研究科, Research Associate (90345041)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Epithelial-Mesenchymal Transtion / EMT / TGF-β / Snail / SIP1 / ZEB1 |
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| Research 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 δEF-1 family proteins, ZEB1 and SIP1, is gradually increased by TGF-β with expression profiles reciprocal to that of E-cadherin. SIP1 or ZEB1 dramatically downregulated the transcription of E-cadherin in NMuMG cells through direct binding to the E-cadherin promoter. Silencing the expression of both SIP1 and ZEB1, but not either alone, by their specific siRNAs completely abolished TGF-β-induced E-cadherin repression. However, mesenchymal markers, including fibronectin, N-cadherin and vimentin, were not affected by knock-down of SIP1 and ZEB1. TGF-β induced the expression of Ets1, which in turn activated the ZEB1 promoter activity. Moreover, upregulation of SIP1 and ZEB1 by TGF-β was suppressed by knock-down of Ets1 expression. In addition, Id2 suppressed the TGF-β- and Ets1-induced upregulation of ZEB1. Taken together, these findings suggest that δEF-1 family proteins, SIP1 and ZEB1, are required, but not sufficient, for TGF-β-induced EMT, and that Ets1 induced by TGF-β may serve as an upstream transcriptional regulator of SIP1 and ZEB1.
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Research Products
(8 results)
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[Journal Article] Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-β signaling2007
Author(s)
Nagano Y, Mavrakis KJ, Lee KL, Fujii T, Koinuma D, Sase H, Yuki K, Isogaya K, Saitoh M, Imamura T, Episkopou V, Miyazono K, Miyazawa K
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Journal Title
J. Biol. Chem. 282
Pages: 20492-20501
Description
「研究成果報告書概要(欧文)」より
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