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beta-cateninA cell–cell adhesion protein that binds to the cytoplasmic domain of E-cadherin. The beta-catenin-cadherin complex recruits alpha-catenin, which in turn binds actin of the cytoskeleton, together forming intercellular adherens junction. Beta-catenin also acts as a component of the Wnt signal transduction pathway, which regulates cell proliferation and differentiation. Tissue concentrations of free beta-catenin are controlled by a protein complex (adenomatous polyposis coli protein and glycogen synthetase kinase3a) which facilitates its breakdown. Wnt inactivates glycogen synthetase kinase3b, allowing beta-catenin to accumulate in cytoplasm and in the nucleus, where it activates the TCF/LEF transcription factors, which in turn act on c-myc, tcf-1 and cyclin D1.
Normal cells show membrane staining for beta-catenin. Beta-catenin expression is regulated by the adenomatous polyposis coli (APC) gene.
Cytoplasmic and/or nuclear staining is abnormal. Mutant CTNNB1 can lead to stabilisation of beta-catenin in the cytoplasm and translocation to the nucleus; disregulation of beta-catenin occurs in Gardner syndrome, leading to familial adenomatous polyposis and fibromatosis. Beta-catenin expression is increased in aggressive fibromatosis, synovial sarcoma, osteosarcoma, liposarcoma and malignant fibrous histiocytoma. High nuclear expression is seen in some mesenchymal tumours; cytoplasmic staining is seen in many. In contrast, cytoplasmic accumulation of beta-catenin is a generally good prognostic marker in upper and lower GI adenocarcinomas.