Document Detail


Wnt/beta-catenin signaling and small molecule inhibitors.
MedLine Citation:
PMID:  23016862     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Andrey Voronkov; Stefan Krauss
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current pharmaceutical design     Volume:  19     ISSN:  1873-4286     ISO Abbreviation:  Curr. Pharm. Des.     Publication Date:  2013  
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-07-08     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  634-64     Citation Subset:  IM    
Affiliation:
SFI-CAST Biomedical Innovation Center, Unit for Cell Signaling, Oslo University Hospital,Forskningsparken, Gaustadalleén 21, 0349, Oslo, Norway. avoron@rr-research.no
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Cell Membrane / physiology
Cell Nucleus / physiology
Cytoplasm / physiology
Drug Design*
Humans
Neoplasms / drug therapy,  pathology
Stem Cells / metabolism
Wnt Proteins / metabolism
Wnt Signaling Pathway / drug effects,  physiology*
beta Catenin / metabolism*
Chemical
Reg. No./Substance:
0/Wnt Proteins; 0/beta Catenin
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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