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Cancer Lett. 2009 Apr 18;276(2):152-9. doi: 10.1016/j.canlet.2008.11.003. Epub 2008 Dec 6.

Dickkopf-4 is frequently down-regulated and inhibits growth of colorectal cancer cells.

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Department of Medicine II, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, Munich, Germany.


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.

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