Modulation of the Canonical Wnt Activity by Androgen Signaling in Prostate Epithelial Basal Stem Cells

January 2020 in “ bioRxiv (Cold Spring Harbor Laboratory) ”

Yueli Liu, Jiawen Wang, Corrigan Horton, Sol Katzman, Tao Cai, Zhu A. Wang

Wnt signaling androgen signaling dihydrotestosterone DHT androgen receptor AR β-catenin

TLDR Androgen signaling reduces Wnt activity, affecting prostate stem cell growth.

The study demonstrated that canonical Wnt signaling was essential for the multipotency of prostate basal stem cells, but ectopic Wnt activity did not induce basal-to-luminal differentiation. Androgen signaling, particularly through dihydrotestosterone (DHT), was found to antagonize Wnt activity, as evidenced by reduced organoid growth and down-regulation of Wnt target genes in the presence of DHT. Molecular analyses indicated that DHT enhanced androgen receptor (AR) and β-catenin binding in the nuclei, suggesting a mechanism for this modulation. The findings highlighted the critical role of AR signaling in regulating Wnt activity and basal cell multipotency in the prostate.

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