Dickkopf-1 antagonizes Wnt signaling independent of β-catenin in human mesothelioma

被引：109

作者：

Lee, AY ^{[1
]}

He, B ^{[1
]}

You, L ^{[1
]}

Xu, ZD ^{[1
]}

Mazieres, J ^{[1
]}

Reguart, N ^{[1
]}

Mikami, I ^{[1
]}

Batra, S ^{[1
]}

Jablons, DM ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Surg, Ctr Comprehens Canc, Thorac Oncol Lab, San Francisco, CA 94115 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 323卷 / 04期

关键词：

Wnt signaling; Wnt antagonist; Dickkopf-1; malignant pleural mesothelioma;

D O I：

10.1016/j.bbrc.2004.09.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Dickkopf-1 (Dkk-1) is a secreted protein that acts as a potent inhibitor of the Wnt signal transduction pathway. It is thought that the antagonistic effect of Dkk-1 is specific to the canonical (Wnt/beta-catenin) pathway. In this study, we demonstrate that restoration of Dkk-1 expression suppresses cell growth and induces apoptotic cell death in beta-catenin-deficient mesothelioma cell lines H28 and MS-1. Furthermore, we found that a small-molecule inhibitor of JNK inhibited the apoptosis induced by Dkk-1 overexpression in these cells. Together, our data suggest that Dkk-1 may be able to antagonize Writ signaling and exert its tumor suppressive effects through beta-catenin-independent non-canonical pathways (i.e., the Wnt/JNK pathway). (C) 2004 Published by Elsevier Inc.

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收藏

页码：1246 / 1250

页数：5

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