title: The significance of the Wnt pathway in the pathology of human cancers.
abstract: The wingless-type (Wnt) signalling transduction pathway is essentially a network of a number of separate but interacting pathways. Specific Wnt ligands bind to their target 'frizzled' membrane receptor and interfere with the multi-protein destruction complex, resulting in downstream activation of gene transcription by beta-catenin. Simplistically, the multi-protein destruction complex involves Axin and APC serving as scaffolds binding both beta-catenin and GSK3, to facilitate phosphorylation of beta-catenin by GSK-3beta. Phosphorylated beta-catenin is degraded in proteasomes by the ubiquination machinery. Unphosphorylated beta-catenin accumulates and associates with nuclear transcription factors leading to the eventual transcription and expression of target genes such as c-myc, c-jun, Fra and cyclin D1. There are several regulatory mechanisms for the down-regulation of the Wnt/beta-catenin signal, perhaps reflecting the pivotal nature of the pathway and the detrimental consequences of inappropriate activation. There has been intense investigation into the role of Wnt genes in human cancer. Although no documentation is made of any mutation or amplification of genes encoding Wnt ligands or receptors linked to human cancer to date, several components of the Wnt pathway have been implicated in carcinogenesis, especially APC and beta-catenin.
authors.affiliation: Department of Anatomical Pathology, Royal Prince Alfred Hospital, University of Sydney NSW Australia. rooshdiya@yahoo.com.au
authors.forename: Rooshdiya
authors.initials: R
authors.lastname: Karim
authors.forename: Gary
authors.initials: G
authors.lastname: Tse
authors.forename: Thomas
authors.initials: T
authors.lastname: Putti
authors.forename: Richard
authors.initials: R
authors.lastname: Scolyer
authors.forename: Soon
authors.initials: S
authors.lastname: Lee
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin