β-catenin signaling and cancer

Abstract

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.