Wnt-β-Catenin

Wnt proteins form a family of highly conserved secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis (embryonic induction, generation of cell polarity, and the specification of cell fate). Mutations in Wnt genes or Wnt pathway components lead to specific developmental defects, while various human diseases, including cancer, are caused by abnormal Wnt signaling. As currently understood, Wnt proteins bind to receptors of the Frizzled and LRP (low density Lipoprotein Receptor-related Protein) families on the cell surface. The result is alleviation of pathway inhibition caused by GSK-3β, APC, and Axin proteins. This stabilizes β-Catenin and promotes its nuclear translocation where it regulates target gene transcription together with Tcf/Lef proteins. During development, the Wnt/β-catenin pathway integrates signals from many other pathways including Retinoic acid, FGF, TGF-β, and BMP in many different cell-types and tissues. In addition, GSK-3β is also involved in glycogen metabolism and other key pathways, which has made its inhibition relevant to diabetes and neurodegenerative disorders[1],[2].