Pathway
Wnt Signalling
Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)
Mechanistic— Decades of developmental and stem-cell biology
What it is
Wnt ligands are secreted glycoproteins that bind Frizzled receptors and LRP5/6 co-receptors. The canonical pathway stabilises β-catenin, which enters the nucleus and drives TCF/LEF-mediated transcription of genes controlling proliferation, stemness, and tissue patterning. Non-canonical Wnt pathways regulate planar cell polarity and Ca2+ signalling.
Why it matters in aging
- Stem-cell niches (intestinal crypts, hair follicle, bone-marrow HSCs, muscle satellite cells) depend on Wnt for self-renewal.
- Bone: Wnt signalling drives osteoblast differentiation; LRP5 gain-of-function variants produce high-bone-mass phenotypes, loss-of-function variants cause osteoporosis-pseudoglioma syndrome.
- Cancer: APC loss (driving constitutive Wnt) is the dominant early event in colorectal cancer.
- Aging signal: serum Wnt antagonists (DKK1, sFRP1, sclerostin) rise with age — possibly contributing to age-related bone loss and stem-cell decline.
Pharmacology
- Romosozumab (anti-sclerostin) increases bone density via Wnt de-repression; approved for severe osteoporosis.
- Porcupine inhibitors (Wnt secretion blockade) in oncology trials.
- β-catenin / TCF inhibitors pre-clinical.
Related entries
References
- Nusse, R. & Clevers, H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 169, 985–999 (2017).