Androgen Action, Wnt Signaling, and Prostate Tumorigenesis

Abstract

Androgen signaling is mainly mediated through AR and plays a critical role in prostate tumorigenesis. Current studies have shown that AR-mediated transcription is facilitated through direct or indirect interactions with different signaling pathways and coregulators. The Wnt signaling pathway and its key component, β-catenin, are critical in embryonic development and tumorigenesis. Emerging evidence suggests a promotional role of the Wnt and β-catenin signaling pathway in prostate cancer development and progression. The discovery of the interaction between AR and β-catenin provides the molecular basis for crosstalk between androgen and Wnt signaling. It has been shown that mutations in adenomatous polyposis coli (APC), β-catenin, and other components of the β-catenin destruction complex are rare in prostate cancer cells. Therefore, the molecular mechanisms underlying β-catenin oncogenic activation in prostate cancer may be different from those observed in human colorectal cancer or other malignancies. Further study of the role and regulation of Wnt signaling and β-catenin should provide fresh insight into our current knowledge of androgen action and prostate tumorigenesis, which may lead to the development of novel therapeutic strategies for prostate cancer patients.