Stromal AR inhibits prostate tumor progression by restraining secretory luminal epithelial cells.

Yueli Liu, Jiawen Wang, Corrigan Horton, Chuan Yu, Beatrice Knudsen, Joshua Stefanson, Kevin Hu, Ofir Stefanson, Jonathan Green, Charlene Guo, Qing Xie, Zhu A Wang

Cell reports 2022 May 24

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Androgen receptor (AR) is expressed in both the prostate epithelium and the prostate stroma and plays diverse roles in prostate physiology. Although low expression of stromal AR is clinically associated with advanced cancer stage and worse outcome, whether stromal AR inhibits or promotes prostate cancer progression remains controversial. Here, we specifically delete AR in smooth muscle cells of the adult mouse prostate under two tumorigenic conditions, namely, the Hi-Myc genetic model and the T + E2 hormonal carcinogenesis model. Histology analyses show that stromal AR deletion exacerbates tumor progression phenotypes in both models. Furthermore, single-cell analyses of the tumor samples reveal that secretory luminal cells are the cell population particularly affected by stromal AR deletion, as they transition to a cellular state of potentiated PI3K-mTORC1 activities. Our results suggest that stromal AR normally inhibits prostate cancer progression by restraining secretory luminal cells and imply possible unintended negative effects of androgen deprivation therapy. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Yueli Liu, Jiawen Wang, Corrigan Horton, Chuan Yu, Beatrice Knudsen, Joshua Stefanson, Kevin Hu, Ofir Stefanson, Jonathan Green, Charlene Guo, Qing Xie, Zhu A Wang. Stromal AR inhibits prostate tumor progression by restraining secretory luminal epithelial cells. Cell reports. 2022 May 24;39(8):110848