The two-handed E box binding zinc finger protein SIP1 downregulates E- cadherin and induces invasion.

Joke Comijn; Geert Berx; Petra Vermassen; Kristin Verschueren; Leonardus Van Grunsven; Erik Bruyneel; Marc Mareel; Danny Huylebroeck; Frans Van Roy

The two-handed E box binding zinc finger protein SIP1 downregulates E- cadherin and induces invasion.

Joke Comijn, Geert Berx, Petra Vermassen, Kristin Verschueren, Leonardus Van Grunsven, Erik Bruyneel, Marc Mareel, Danny Huylebroeck, Frans Van Roy

Cell Biology and Histology

Research output: Contribution to journal › Article › peer-review

1216 Citations (Scopus)

Abstract

Transcriptional downregulation of E-cadherin appears to be an important event in the progression of various epithelial tumors. SIP1 (ZEB-2) is a Smad-interacting, multi-zinc finger protein that shows specific DNA binding activity. Here, we report that expression of wild-type but not of mutated SIP1 downregulates mammalian E-cadherin transcription via binding to both conserved E2 boxes of the minimal E-cadherin promoter. SIP1 and Snail bind to partly overlapping promoter sequences and showed similar silencing effects. SIP1 can be induced by TGF-beta treatment and shows high expression in several E-cadherin-negative human carcinoma cell lines. Conditional expression of SIP1 in E-cadherin-positive MDCK cells abrogates E-cadherin-mediated intercellular adhesion and simultaneously induces invasion. SIP1 therefore appears to be a promoter of invasion in malignant epithelial tumors.

Original language	English
Pages (from-to)	1267-1278
Number of pages	12
Journal	Molecular Cell
Issue number	7
Publication status	Published - 2001

Keywords

sip1

Cite this

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title = "The two-handed E box binding zinc finger protein SIP1 downregulates E- cadherin and induces invasion.",

abstract = "Transcriptional downregulation of E-cadherin appears to be an important event in the progression of various epithelial tumors. SIP1 (ZEB-2) is a Smad-interacting, multi-zinc finger protein that shows specific DNA binding activity. Here, we report that expression of wild-type but not of mutated SIP1 downregulates mammalian E-cadherin transcription via binding to both conserved E2 boxes of the minimal E-cadherin promoter. SIP1 and Snail bind to partly overlapping promoter sequences and showed similar silencing effects. SIP1 can be induced by TGF-beta treatment and shows high expression in several E-cadherin-negative human carcinoma cell lines. Conditional expression of SIP1 in E-cadherin-positive MDCK cells abrogates E-cadherin-mediated intercellular adhesion and simultaneously induces invasion. SIP1 therefore appears to be a promoter of invasion in malignant epithelial tumors.",

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author = "Joke Comijn and Geert Berx and Petra Vermassen and Kristin Verschueren and {Van Grunsven}, Leonardus and Erik Bruyneel and Marc Mareel and Danny Huylebroeck and {Van Roy}, Frans",

year = "2001",

language = "English",

pages = "1267--1278",

journal = "Molecular Cell",

issn = "1097-2765",

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The two-handed E box binding zinc finger protein SIP1 downregulates E- cadherin and induces invasion. / Comijn, Joke; Berx, Geert; Vermassen, Petra; Verschueren, Kristin; Van Grunsven, Leonardus; Bruyneel, Erik; Mareel, Marc; Huylebroeck, Danny; Van Roy, Frans.

In: Molecular Cell, No. 7, 2001, p. 1267-1278.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The two-handed E box binding zinc finger protein SIP1 downregulates E- cadherin and induces invasion.

AU - Comijn, Joke

AU - Berx, Geert

AU - Vermassen, Petra

AU - Verschueren, Kristin

AU - Van Grunsven, Leonardus

AU - Bruyneel, Erik

AU - Mareel, Marc

AU - Huylebroeck, Danny

AU - Van Roy, Frans

PY - 2001

Y1 - 2001

N2 - Transcriptional downregulation of E-cadherin appears to be an important event in the progression of various epithelial tumors. SIP1 (ZEB-2) is a Smad-interacting, multi-zinc finger protein that shows specific DNA binding activity. Here, we report that expression of wild-type but not of mutated SIP1 downregulates mammalian E-cadherin transcription via binding to both conserved E2 boxes of the minimal E-cadherin promoter. SIP1 and Snail bind to partly overlapping promoter sequences and showed similar silencing effects. SIP1 can be induced by TGF-beta treatment and shows high expression in several E-cadherin-negative human carcinoma cell lines. Conditional expression of SIP1 in E-cadherin-positive MDCK cells abrogates E-cadherin-mediated intercellular adhesion and simultaneously induces invasion. SIP1 therefore appears to be a promoter of invasion in malignant epithelial tumors.

AB - Transcriptional downregulation of E-cadherin appears to be an important event in the progression of various epithelial tumors. SIP1 (ZEB-2) is a Smad-interacting, multi-zinc finger protein that shows specific DNA binding activity. Here, we report that expression of wild-type but not of mutated SIP1 downregulates mammalian E-cadherin transcription via binding to both conserved E2 boxes of the minimal E-cadherin promoter. SIP1 and Snail bind to partly overlapping promoter sequences and showed similar silencing effects. SIP1 can be induced by TGF-beta treatment and shows high expression in several E-cadherin-negative human carcinoma cell lines. Conditional expression of SIP1 in E-cadherin-positive MDCK cells abrogates E-cadherin-mediated intercellular adhesion and simultaneously induces invasion. SIP1 therefore appears to be a promoter of invasion in malignant epithelial tumors.

KW - sip1

M3 - Article

SP - 1267

EP - 1278

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 7

ER -

The two-handed E box binding zinc finger protein SIP1 downregulates E- cadherin and induces invasion.

Abstract

Keywords

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