The WNT signaling pathway from ligand secretion to gene transcription: Molecular mechanisms and pharmacological targets

被引：134
作者：
Baarsma, Hoeke A. [1 ,2 ,3 ]
Koenigshoff, Melanie [2 ,3 ]
Gosens, Reinoud [1 ]
机构：
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Mol Pharmacol, GRIAC Res Inst, NL-9713 AV Groningen, Netherlands
[2] Univ Munich, Univ Hosp Grosshadern, Comprehens Pneumol Ctr, Munich, Germany
[3] Helmholtz Zentrum Munchen, Munich, Germany
来源：
PHARMACOLOGY & THERAPEUTICS | 2013年 / 138卷 / 01期
基金：
欧洲研究理事会;
关键词：
beta-Catenin; Frizzled (FZD); Lipoprotein receptor related proteins (LRP); Axin; Casein kinase (CK); Dishevelled (DVL); FRIZZLED-RELATED PROTEIN-1; SYNTHASE KINASE 3-BETA; CATENIN DESTRUCTION COMPLEX; RECEPTOR-RELATED PROTEIN-5; CYSTEINE-RICH DOMAIN; APC TUMOR-SUPPRESSOR; BETA-CATENIN; NUCLEAR-LOCALIZATION; TCF/BETA-CATENIN; SMOOTH-MUSCLE;
D O I：
10.1016/j.pharmthera.2013.01.002
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Wingless/integrase-1 (WNT) signaling is a key pathway regulating various aspects of embryonic development; however it also underlies several pathological conditions in man, including various cancers and fibroproliferative diseases in several organs. Investigating the molecular processes involved in (canonical) WNT signaling will open new avenues for generating new therapeutics to specifically target diseases in which WNT signaling is aberrantly regulated. Here we describe the complexity of WNT signal transduction starting from the processes involved in WNT ligand biogenesis and secretion by WNT producing cells followed by a comprehensive overview of the molecular signaling events ultimately resulting in enhanced transcription of specific genes in WNT receiving cells. Finally, the possible targets for therapeutic intervention and the available pharmacological inhibitors for this complex signaling pathway are discussed. (C) 2013 Elsevier Inc. All rights reserved.
引用
收藏
页码：66 / 83
页数：18
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