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E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer

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Abstract

The embryonic program ‘epithelial-mesenchymal transition’ (EMT) is activated during tumor invasion in disseminating cancer cells. Characteristic to these cells is a loss of E-cadherin expression, which can be mediated by EMT-inducing transcriptional repressors, e.g. ZEB1. Consequences of a loss of E-cadherin are an impairment of cell-cell adhesion, which allows detachment of cells, and nuclear localization of β-catenin. In addition to an accumulation of cancer stem cells, nuclear β-catenin induces a gene expression pattern favoring tumor invasion, and mounting evidence indicates multiple reciprocal interactions of E-cadherin and β-catenin with EMT-inducing transcriptional repressors to stabilize an invasive mesenchymal phenotype of epithelial tumor cells.

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Acknowledgements

This work was supported by grants to T.B. from the EU MCSC contract no. 037297, the DFG (no. BR 1399/4-3) and the Deutsche Krebshilfe (no. 106958).

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  1. Department of Visceral Surgery, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany

    Otto Schmalhofer, Simone Brabletz & Thomas Brabletz

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  1. Otto Schmalhofer
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  2. Simone Brabletz
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  3. Thomas Brabletz
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Correspondence to Thomas Brabletz.

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Schmalhofer, O., Brabletz, S. & Brabletz, T. E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev 28, 151–166 (2009). https://doi.org/10.1007/s10555-008-9179-y

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  • DOI: https://doi.org/10.1007/s10555-008-9179-y

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