Dickkopf-4 is frequently down-regulated and inhibits growth of colorectal cancer cells
Dickkopf-4 is frequently down-regulated and inhibits growth of colorectal cancer cells
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DOI：
10.1016/j.canlet.2008.11.003
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发表时间：
2009-04-18
期刊：
影响因子：
9.7
通讯作者：
Kolligs, Frank T.
中科院分区：
文献类型：
--
作者：
Baehs, Sebastian;Herbst, Andreas;Kolligs, Frank T.
与 Dickkopf-1 (DKK1) 一样，DKK4 是结直肠癌中 β-catenin/Tcf-4 的靶标。然而，作为 Wnt 信号传导的负调节因子，其在结直肠癌细胞中的功能尚不清楚。我们报告说，DKK4 在 β-catenin/Tcf-4 失调的结直肠癌细胞系和原发性结直肠癌中经常下调。癌细胞暴露于 DKK4 会强烈抑制基础 β-catenin/Tcf-4 信号传导活性、癌细胞生长和细胞周期进程。因此，这种负反馈环路的丧失为表达 Wnt 因子的癌细胞提供了生长优势。我们的数据表明 DKK4 是结肠癌细胞生长的重要负调节因子。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
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.