Journal
CANCER LETTERS
Volume 276, Issue 2, Pages 152-159Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.11.003
Keywords
beta-catenin; Wnt; Dickkopf; DKK4; Colorectal cancer
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Funding
- Deutsche Forschungsgemeinschaft [KO1826/3, GO417/4]
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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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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