β-catenin signaling and cancer^†

Since its discovery as a protein associated with the cytoplasmic region of E-cadherin, β-catenin has been shown to perform two apparently unrelated functions: it has a crucial role in cell–cell adhesion in addition to a signaling role as a component of the Wnt/wg pathway. Wnt/wg signaling results in β-catenin accumulation and transcriptional activation of specific target genes during development. It is now apparent that deregulation of β-catenin signaling is an important event in the genesis of a number of malignancies, such as colon cancer, melanoma, hepatocellular carcinoma, ovarian cancer, endometrial cancer, medulloblastoma pilomatricomas, and prostate cancer. β-catenin mutations appear to be a crucial step in the progression of a subset of these cancers, suggesting an important role in the control of cellular proliferation or cell death. The APC/β-catenin pathway is highly regulated and includes players such as GSK3-β, CBP, Groucho, Axin, Conductin, and TCF. c-MYC and cyclin D1 were recently identified as a key transcriptional targets of this pathway and additional targets are likely to emerge. BioEssays 21:1021–1030, 1999. Published 1999 John Wiley & Sons, Inc.