The Transcriptional Repressor ZEB1 Promotes Metastasis and Loss of Cell Polarity in Cancer
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- Simone Spaderna
- 1Department of Visceral Surgery, University of Freiburg, Freiburg, Germany;
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- Otto Schmalhofer
- 1Department of Visceral Surgery, University of Freiburg, Freiburg, Germany;
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- Mandy Wahlbuhl
- 2Department of Pathology and
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- Arno Dimmler
- 2Department of Pathology and
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- Katja Bauer
- 3Nikolaus-Fiebiger-Center, University of Erlangen, Erlangen, Germany;
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- Aneesa Sultan
- 4Max F. Perutz Laboratories, Medical University Vienna, Vienna, Austria;
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- Falk Hlubek
- 5Department of Pathology, University of Munchen, Munich, Germany; and
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- Andreas Jung
- 5Department of Pathology, University of Munchen, Munich, Germany; and
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- Dennis Strand
- 6First Department of Internal Medicine, University of Mainz, Mainz, Germany
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- Andreas Eger
- 4Max F. Perutz Laboratories, Medical University Vienna, Vienna, Austria;
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- Thomas Kirchner
- 5Department of Pathology, University of Munchen, Munich, Germany; and
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- Jürgen Behrens
- 3Nikolaus-Fiebiger-Center, University of Erlangen, Erlangen, Germany;
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- Thomas Brabletz
- 1Department of Visceral Surgery, University of Freiburg, Freiburg, Germany;
説明
<jats:title>Abstract</jats:title> <jats:p>Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program “epithelial-mesenchymal transition” (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity. Thereby, ZEB1 suppresses the expression of cell polarity factors, in particular of Lgl2, which we found reduced in colorectal and breast cancers. We further show that retention of Lgl2 expression is critical for the epithelial phenotype and that its loss might be involved in metastasis. Thus, by linking EMT, loss of polarity, and metastasis, ZEB1 is a crucial promoter of malignant tumor progression. [Cancer Res 2008;68(2):537–44]</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 68 (2), 537-544, 2008-01-15
American Association for Cancer Research (AACR)
