Stromal AR inhibits prostate tumor progression by restraining secretory luminal epithelial cells.
Stromal AR inhibits prostate tumor progression by restraining secretory luminal epithelial cells.
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DOI：
10.1016/j.celrep.2022.110848
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发表时间：
2022-05-24
期刊：
影响因子：
8.8
通讯作者：
Wang, Zhu A.
中科院分区：
文献类型：
--
作者：
Liu, Yueli;Wang, Jiawen;Horton, Corrigan;Yu, Chuan;Knudsen, Beatrice;Stefanson, Joshua;Hu, Kevin;Stefanson, Ofir;Green, Jonathan;Guo, Charlene;Xie, Qing;Wang, Zhu A.
雄激素受体（AR）在前列腺上皮和前列腺基质中表达，并在前列腺生理学中发挥多种作用。尽管间质 AR 的低表达在临床上与晚期癌症阶段和较差的结果相关，但间质 AR 是否抑制或促进前列腺癌进展仍存在争议。在这里，我们特意删除了两种致瘤条件下成年小鼠前列腺平滑肌细胞中的AR，即Hi-Myc遗传模型和T + E2激素致癌模型。组织学分析表明，基质 AR 缺失会加剧两种模型中的肿瘤进展表型。此外，肿瘤样本的单细胞分析表明，分泌性管腔细胞是特别受基质 AR 缺失影响的细胞群，因为它们转变为 PI3K-mTORC1 活性增强的细胞状态。我们的结果表明，基质 AR 通常通过抑制分泌管腔细胞来抑制前列腺癌的进展，这意味着雄激素剥夺疗法可能会产生意想不到的负面影响。基质雄激素受体（AR）是否促进或抑制前列腺癌进展存在争议。刘等人。报道称，平滑肌细胞中 AR 的缺失会增强管腔上皮细胞亚群中 PI3K 通路的活性，从而加剧肿瘤表型，这表明 AR 在前列腺基质中具有抑制肿瘤的作用。
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. Whether stromal androgen receptor (AR) promotes or inhibits prostate cancer progression is controversial. Liu et al. report that AR loss in smooth muscle cells exacerbates tumor phenotypes by potentiating the PI3K pathway activity in a subset of luminal epithelial cells, suggesting a tumor-suppressing role for AR in the prostate stroma.
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影响因子：
5.2
作者：
Leach DA;Buchanan G
通讯作者：
Buchanan G
DOI：
10.1073/pnas.0308114100
发表时间：
2004-02-03
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
--
作者：
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通讯作者：
Huidobro, C
影响因子：
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作者：
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通讯作者：
Schroder, FH
影响因子：
7.7
作者：
Chua CW;Epsi NJ;Leung EY;Xuan S;Lei M;Li BI;Bergren SK;Hibshoosh H;Mitrofanova A;Shen MM
通讯作者：
Shen MM