title: Wnt/beta-catenin signaling and small molecule inhibitors.
abstract: Wnt/β-catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/β-catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, β-catenin, serves several cellular functions. It functions in a dynamic mode at multiple cellular locations, including the plasma membrane, where β-catenin contributes to the stabilization of intercellular adhesive complexes, the cytoplasm where β-catenin levels are regulated and the nucleus where β-catenin is involved in transcriptional regulation and chromatin interactions. Central effectors of β-catenin levels are a family of cysteine-rich secreted glycoproteins, known as Wnt morphogens. Through the LRP5/6-Frizzled receptor complex, Wnts regulate the location and activity of the destruction complex and consequently intracellular β- catenin levels. However, β-catenin levels and their effects on transcriptional programs are also influenced by multiple other factors including hypoxia, inflammation, hepatocyte growth factor-mediated signaling, and the cell adhesion molecule E-cadherin. The broad implications of Wnt/β-catenin signaling in development, in the adult body and in disease render the pathway a prime target for pharmacological research and development. The intricate regulation of β-catenin at its various locations provides alternative points for therapeutic interventions.
authors.affiliation: SFI-CAST Biomedical Innovation Center, Unit for Cell Signaling, Oslo University Hospital,Forskningsparken, Gaustadalleén 21, 0349, Oslo, Norway. avoron@rr-research.no
authors.forename: Andrey
authors.initials: A
authors.lastname: Voronkov
authors.forename: Stefan
authors.initials: S
authors.lastname: Krauss
mesh_terms: D000328:Adult; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D003593:Cytoplasm / Q000502:physiology; D015195:Drug Design; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin