A Tale of Two Signals: AR and WNT in Development and Tumorigenesis of Prostate and Mammary GlandReport as inadecuate


A Tale of Two Signals: AR and WNT in Development and Tumorigenesis of Prostate and Mammary Gland


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1

Division of Genetics, Brigham and Women’s Hospital, 77 Avenue Louis Pasteur, Room 466, Boston, MA 02115, USA

2

Department of Medicine, Harvard Medical School, Boston, MA 02115, USA





*

Author to whom correspondence should be addressed.



Academic Editor: Emmanuel S. Antonarakis

Abstract Prostate cancer PCa is one of the most common cancers and among the leading causes of cancer deaths for men in industrialized countries. It has long been recognized that the prostate is an androgen-dependent organ and PCa is an androgen-dependent disease. Androgen action is mediated by the androgen receptor AR. Androgen deprivation therapy ADT is the standard treatment for metastatic PCa. However, almost all advanced PCa cases progress to castration-resistant prostate cancer CRPC after a period of ADT. A variety of mechanisms of progression from androgen-dependent PCa to CRPC under ADT have been postulated, but it remains largely unclear as to when and how castration resistance arises within prostate tumors. In addition, AR signaling may be modulated by extracellular factors among which are the cysteine-rich glycoproteins WNTs. The WNTs are capable of signaling through several pathways, the best-characterized being the canonical WNT-β-catenin-TCF-mediated canonical pathway. Recent studies from sequencing PCa genomes revealed that CRPC cells frequently harbor mutations in major components of the WNT-β-catenin pathway. Moreover, the finding of an interaction between β-catenin and AR suggests a possible mechanism of cross talk between WNT and androgen-AR signaling pathways. In this review, we discuss the current knowledge of both AR and WNT pathways in prostate development and tumorigenesis, and their interaction during development of CRPC. We also review the possible therapeutic application of drugs that target both AR and WNT-β-catenin pathways. Finally, we extend our review of AR and WNT signaling to the mammary gland system and breast cancer. We highlight that the role of AR signaling and its interaction with WNT signaling in these two hormone-related cancer types are highly context-dependent. View Full-Text

Keywords: androgen receptor; AR; WNT; prostate; prostate cancer; castration-resistant prostate cancer; CRPC; mammary gland; breast cancer androgen receptor; AR; WNT; prostate; prostate cancer; castration-resistant prostate cancer; CRPC; mammary gland; breast cancer





Author: Hubert Pakula 1,2, Dongxi Xiang 1,2 and Zhe Li 1,2,*

Source: http://mdpi.com/



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