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

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139 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)66-83
Number of pages18
JournalPharmacology & Therapeutics
Volume138
Issue number1
DOIs
Publication statusPublished - Apr-2013

Keywords

  • beta-Catenin
  • Frizzled (FZD)
  • Lipoprotein receptor related proteins (LRP)
  • Axin
  • Casein kinase (CK)
  • Dishevelled (DVL)
  • GLYCOGEN-SYNTHASE KINASE-3
  • FRIZZLED-RELATED PROTEIN-1
  • IDIOPATHIC PULMONARY-FIBROSIS
  • CATENIN DESTRUCTION COMPLEX
  • RECEPTOR-RELATED PROTEIN-5
  • CYSTEINE-RICH DOMAIN
  • APC TUMOR-SUPPRESSOR
  • HUMAN COLON-CANCER
  • BETA-CATENIN
  • NUCLEAR-LOCALIZATION

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