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

被引：40
|
作者：
Baehs, Sebastian [1 ]
Herbst, Andreas [1 ]
Thieme, Susanne E. [2 ]
Perschl, Claudia [1 ]
Behrens, Andrea [1 ]
Scheel, Silvio [3 ]
Jung, Andreas [3 ]
Brabletz, Thomas [4 ]
Goeke, Burkhard [1 ]
Blum, Helmut [2 ]
Kolligs, Frank T. [1 ]
机构：
[1] Univ Munich, Klinikum Grosshadern, Dept Med 2, D-81377 Munich, Germany
[2] Univ Munich, Gene Ctr, LAFUGA, D-81377 Munich, Germany
[3] Univ Munich, Inst Pathol, D-80337 Munich, Germany
[4] Univ Freiburg, Dept Surg, D-79095 Freiburg, Germany
来源：
CANCER LETTERS | 2009年 / 276卷 / 02期
关键词：
beta-catenin; Wnt; Dickkopf; DKK4; Colorectal cancer; WNT SIGNALING PATHWAY; HUMAN COLON-CANCER; EPIGENETIC INACTIVATION; BETA-CATENIN/TCF; FAMILY; GENES; MUTATIONS; TARGET;
D O I：
10.1016/j.canlet.2008.11.003
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：152 / 159
页数：8
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