Wnt Pathway

Abstract

The term Wnt was forged by contraction of Win gless-type mouse mammary tumour virus int egration site after the discovery on a viral oncogene in mice which was homologous to a mutant Drosophila gene. The Wnt pathway, especially under its canonical form (Wnt–β-catenin pathway), is a signalling pathway involved in vertebrate and invertebrate development. It plays a major role in embryogenesis and morphogenesis and in stem cell commitment to differentiation or proliferation. This pathway is relatively complex, and all its processes and physiological roles are not completely deciphered. The proteins involved in this pathway are called ‘Wingless’, ‘Frizzled’, ‘Dishevelled’, which originally designated the mutants of Drosophila development and demonstrates the universality of this pathway in the animal kingdom. Germline alterations of this pathway in humans determine congenital hereditary diseases, and some somatic and germinal alterations are associated with oncogenesis.

Briefly, protein messengers called WNT activate GPCR-related membrane receptors called Frizzled (FZD), and this activation leads to the stabilisation of the cytoplasmic form of a protein involved in intercellular junctions of epithelial tissues, β-catenin. The stabilised protein can then be transferred into the nucleus where it activates transcription programmes of numerous genes, especially those encoding the proteins required for cell proliferation and cell cycle entry (cyclin D, MYC, etc.).