Wnt signaling

Wnt signaling is a family of evolutionarily conserved intercellular communication pathways initiated by secreted Wnt glycolipoproteins binding to Frizzled receptors, with the canonical (β-catenin-dependent) branch being the most studied. In the absence of Wnt ligands, a destruction complex containing APC, Axin, GSK-3β and CK1 phosphorylates β-catenin, targeting it for proteasomal degradation; Wnt binding stabilises β-catenin, which then translocates to the nucleus to drive TCF/LEF target gene transcription. Wnt signaling is essential for stem cell self-renewal, tissue regeneration, and bone homeostasis, but its activity declines in aged tissues such as skeletal muscle, intestinal crypts, and the bone marrow niche, contributing to stem cell exhaustion; conversely, dysregulated Wnt activity is a driver of cancer and tissue fibrosis in other contexts.