Abstract
Plakophilin 3 (PKP3) belongs to the p120ctn family of armadillo-related proteins predominantly functioning in desmosome formation. Here we report that PKP3 is transcriptionally repressed by the E-cadherin repressor ZEB1 in metastatic cancer cells. ZEB1 physically associates with two conserved E-box elements in the PKP3 promoter and partially represses the activity of corresponding human and mouse PKP3 promoter fragments in reporter gene assays. In human tumours ZEB1 is upregulated in invasive cancer cells at the tumour-host interface, which is accompanied by downregulation of PKP3 expression levels. Hence, the transcriptional repression of PKP3 by ZEB1 contributes to ZEB1-mediated disintegration of intercellular adhesion and epithelial to mesenchymal transition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Cadherins / metabolism
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Disease Progression
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Gene Expression Regulation, Neoplastic*
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Homeodomain Proteins / analysis
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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Mice
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Neoplasm Invasiveness
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Neoplasms / chemistry
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Neoplasms / genetics
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Neoplasms / pathology*
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Plakophilins / analysis
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Plakophilins / genetics*
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Promoter Regions, Genetic
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Repressor Proteins / analysis
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Transcription Factors / analysis
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Tumor Cells, Cultured
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Zinc Finger E-box-Binding Homeobox 1
Substances
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Cadherins
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Homeodomain Proteins
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PKP3 protein, human
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Plakophilins
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Repressor Proteins
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Transcription Factors
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ZEB1 protein, human
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Zinc Finger E-box-Binding Homeobox 1