Roles and regulation of Wnt signaling and beta-catenin in prostate cancer.

The Wnt signaling pathway and its key component beta-catenin play critical roles in embryonic development as well as in human diseases, including various malignancies. Accumulated evidence has demonstrated a significant role for the Wnt pathway in the development and progression of human prostate cancer. The recent discovery of an interaction between beta-catenin and the androgen receptor (AR) suggests a possible mechanism of cross talk between Wnt and androgen signaling pathways. In this review, we summarize the recent progresses in this interesting and growing field. Particularly, we focus on the observation that the activation of the Wnt-mediated signal occurs in a different manner in prostate cancer than in colorectal cancer or other human malignancies. Since mutations in Adenomatous polyposis coli (APC), beta-catenin, and other components of the beta-catenin destruction complex are rare in prostate cancer cells, other regulatory mechanisms appear to play dominant roles in the activation of beta-catenin, such as loss or reduction of E-cadherin, a component of cell adhesion complex, and abnormal expression of Wnt ligands, receptors, inhibitors, and other co-regulators. Understanding the role and regulation of the Wnt signaling pathway in prostate cancer cells may help identify new targets for the prostate cancer therapy.