Department of Molecular Pharmacology, GRIAC research institute, University of Groningen, Groningen, The Netherlands.
Pharmacol Ther. 2013 Apr;138(1):66-83. doi: 10.1016/j.pharmthera.2013.01.002. Epub 2013 Jan 14.
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.
Wnt/整合素-1（WNT）信号通路是调节胚胎发育各个方面的关键途径；然而，它也存在于人类的几种病理状况下，包括几种器官中的各种癌症和纤维增生性疾病。研究（经典）WNT 信号通路所涉及的分子过程将为开发新的治疗方法开辟新的途径，以专门针对 WNT 信号通路异常调节的疾病。在这里，我们从 WNT 产生细胞参与 WNT 配体生物发生和分泌的过程开始，描述了 WNT 信号转导的复杂性，然后全面概述了最终导致 WNT 受体细胞中特定基因转录增强的分子信号事件。最后，讨论了该复杂信号通路的治疗干预的可能靶点和可用的药理学抑制剂。
