Wnt/beta-Catenin Signaling and Small Molecule Inhibitors (original) (raw)
Wnt/-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/-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,-catenin, serves several cellular functions. It functions in a dynamic mode at multiple cellular locations , including the plasma membrane, where-catenin contributes to the stabilization of intercellular adhesive complexes, the cytoplasm where-catenin levels are regulated and the nucleus where-catenin is involved in transcriptional regulation and chromatin interactions. Central effectors of-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-catenin levels. However,-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/-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-catenin at its various locations provides alternative points for therapeutic interventions.
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