Protein Wnt-10b (WNT10B)

Protein Wnt-10b is a secreted glycoprotein belonging to the highly conserved Wnt family of signaling proteins, which play fundamental roles in embryonic development and adult tissue homeostasis (UniProt). It primarily functions as a ligand that activates the canonical Wnt/beta-catenin signaling pathway by binding to Frizzled receptors and LRP5/6 co-receptors, leading to the stabilization and nuclear translocation of beta-catenin (PubMed). WNT10B is a critical regulator of mesenchymal stem cell fate, acting as a master switch that promotes osteoblast differentiation (bone formation) while actively suppressing adipogenesis (fat formation) (PMC). In clinical contexts, aberrant WNT10B expression is strongly linked to various pathologies; its overexpression is observed in cancers such as triple-negative breast cancer and osteosarcoma, where it drives tumor progression and metastasis (NIH). Conversely, loss-of-function mutations or reduced signaling are associated with bone density disorders like osteoporosis and developmental defects such as split-hand/foot malformation (OMIM). Therapeutic targeting of WNT10B involves the use of Porcupine inhibitors to block its secretion in oncology or the development of pathway activators to treat degenerative bone diseases (Journal of Medicinal Chemistry).

Other names

WNT-12SHFM6STHAG8Wnt family member 10BSplit-hand/foot malformation 6

WNT10B acts as an extracellular ligand that binds to Frizzled (FZD) receptors and Low-density lipoprotein receptor-related protein 5/6 (LRP5/6) co-receptors. This interaction inhibits the beta-catenin destruction complex (comprising Axin, APC, and GSK3), allowing beta-catenin to accumulate in the cytoplasm and translocate to the nucleus. Once in the nucleus, beta-catenin complexes with TCF/LEF transcription factors to initiate the expression of target genes involved in cell growth and differentiation.