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Wnt Pathway | History





  • While looking for the cellular genes responsible for mouse mammary tumor virus (MMTV) oncogenesis, researchers identified the int1 gene
  • Researchers confirmed that int1 was a proto-oncogene—a gene that, when altered, can initiate tumorigenesis—by studying its role in mouse models
  • Roel Nusse and Harold Varmus discovered an int1 homologue—Wingless (Wg)—in Drosophila, leading to the realization of its importance in the development of tissues
  • Researchers found additional homologues of int1, and then classified the entire family of genes as the “Wnt” family (for Wingless-related integration site). The int1 gene was then renamed Wnt1



  • Further research suggested that interactions among several Wnt signaling pathway components were involved in cell growth and tumorigenesis
  • A preliminary outline of the Wnt signaling pathway was drafted, and some key proteins were identified; however, there were still important gaps in the understanding of the pathway
  • By the end of the 20th century, researchers had constructed a detailed blueprint of the Wnt signaling pathway



  • Ongoing research continues to implicate Wnt signaling in cancer and in a growing list of degenerative and metabolic diseases, including osteoarthritis, osteoporosis, and androgenetic alopecia

References: 1. Nusse R, Varmus H. Three decades of Wnts: a personal perspective on how a scientific field developed. EMBO J. 2012;31(12):2670-2684. 2. Anastas JN, Moon RT. WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 2013;13(1):11-26. 3. Zhou Y, Wang T, Hamilton JL, Chen D. Wnt/β-catenin signaling in osteoarthritis and in other forms of arthritis. Curr Rheumatol Rep. 2017;19(9):53. doi:10.1007/s11926-017-0679-z. 4. Manolagas SC. Wnt signaling and osteoporosis. Maturitas. 2014;78(3):233-237. 5. Chun JS, Oh H, Yang S, Park M. Wnt signaling in cartilage development and degeneration. BMB Rep. 2008;41(7):485-494. 6. Leirós GJ, Attorresi AI, Balañá ME. Hair follicle stem cell differentiation is inhibited through cross-talk between Wnt/β-catenin and androgen signalling in dermal papilla cells from patients with androgenetic alopecia. Br J Dermatol. 2012;166(5):1035-1042.