Abstract
Like Dickkopf-1 (DKK1), DKK4 is a target of beta-catenin/Tcf-4 in colorectal cancer. However, as a negative regulator of Wnt signalling its function in colorectal cancer cells is not well understood. We report that DKK4 is frequently down-regulated in colorectal cancer cell lines with deregulated beta-catenin/Tcf-4 and in primary colorectal cancers. Exposure of cancer cells to DKK4 strongly inhibits basal beta-catenin/Tcf-4 signalling activity, cancer cell growth and cell cycle progression. Therefore, loss of this negative feed-back loop provides Wnt factor expressing cancer cells with a growth advantage. Our data demonstrate that DKK4 is an important negative regulator of colon cancer cell growth.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Cell Line, Tumor
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Cell Proliferation
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Colorectal Neoplasms / pathology
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Colorectal Neoplasms / prevention & control*
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DNA-Binding Proteins / antagonists & inhibitors
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Down-Regulation
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Epigenesis, Genetic
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / physiology*
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Promoter Regions, Genetic
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Signal Transduction
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Transcription Factor 4
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Transcription Factors / antagonists & inhibitors
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beta Catenin / antagonists & inhibitors
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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DKK4 protein, human
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DNA-Binding Proteins
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Intercellular Signaling Peptides and Proteins
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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beta Catenin