Abstract
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.
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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Breast Neoplasms / pathology*
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Carcinoma / pathology*
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Cell Polarity / genetics*
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Colorectal Neoplasms / pathology*
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Gene Expression Regulation, Neoplastic
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HCT116 Cells
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Homeodomain Proteins / antagonists & inhibitors
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Homeodomain Proteins / physiology*
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Humans
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Liver Neoplasms / secondary
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Molecular Sequence Data
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Neoplasm Metastasis
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Neoplasm Transplantation
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RNA Interference / physiology
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Repressor Proteins / antagonists & inhibitors
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Repressor Proteins / physiology
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Sequence Homology, Nucleic Acid
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / physiology*
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Transplantation, Heterologous
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Zinc Finger E-box-Binding Homeobox 1
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beta Karyopherins / genetics
Substances
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Homeodomain Proteins
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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
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beta Karyopherins
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late gestation lung 2 karyopherin