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.
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:comment |
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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| skos:exactMatch | |
| uniprot:name |
Mol. Cell
|
| uniprot:author |
Berx G.,
Bruyneel E.,
Comijn J.,
Huylebroeck D.,
Mareel M.,
Vermassen P.,
Verschueren K.,
van Grunsven L.,
van Roy F.
|
| uniprot:date |
2001
|
| uniprot:pages |
1267-1278
|
| uniprot:title |
The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion.
|
| uniprot:volume |
7
|
| dc-term:identifier |
doi:10.1016/S1097-2765(01)00260-X
|