ArticlePLoS genetics2020
Loss of androgen signaling in mesenchymal sonic hedgehog responsive cells diminishes prostate development, growth, and regeneration.
Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Melatonin modulates SHH/GLI3 signaling and placental angiogenesis to counter acrylamide embryotoxicity.Journal of molecular histology · 2025Article
- Visualizing androgen signaling and assessing its interaction with canonical Wnt signaling pathways in prostate development, morphogenesis, and regeneration.PLoS genetics · 2025Article
- Interactions between androgen and IGF1 axes in prostate tumorigenesis.Nature reviews. Urology · 2025Review
- Tracing the Evolution of Sex Hormones and Receptor-Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Dorsomorphin Suppresses EMT to Reduce AR-Negative Prostate Cancer Metastasis by Synergistically Antagonizing JAK2/STAT3 and Gli2-Independent Shh Activation.Prostate cancer · 2025Article
- Stromal androgen signaling governs essential niches in supporting prostate development and tumorigenesis.Oncogene · 2024Review
- Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis.Nature communications · 2022Article
- The anti-inflammatory properties of the methanolic extract ofSaudi journal of biological sciences · 2022Article
- Canonical Hedgehog Pathway and Noncanonical GLI Transcription Factor Activation in Cancer.Cells · 2022Review
- Prostate organogenesis.Development (Cambridge, England) · 2022Article
- Role of prostate stem cells and treatment strategies in benign prostate hyperplasia.American journal of clinical and experimental urology · 2022Review
- The most effective but largely ignored target for prostate cancer early detection and intervention.Journal of Cancer · 2022Article
- Stromal androgen and hedgehog signaling regulates stem cell niches in pubertal prostate development.Development (Cambridge, England) · 2021Article
- Developmental expression patterns of toolkit genes in male accessory gland of Drosophila parallels those of mammalian prostate.Biology open · 2021Article
- Smoothened loss is a characteristic of neuroendocrine prostate cancer.The Prostate · 2021Article
- Sonic Hedgehog signaling pathway in gynecological and genitourinary cancer (Review).International journal of molecular medicine · 2021Review
- Inadvertent nucleotide sequence alterations during mutagenesis: highlighting the vulnerabilities in mouse transgenic technology.Journal, genetic engineering & biotechnology · 2021Article
- Androgen action in cell fate and communication during prostate development at single-cell resolution.Development (Cambridge, England) · 2021Article
- Prostate cancer management: long-term beliefs, epidemic developments in the early twenty-first century and 3PM dimensional solutions.The EPMA journal · 2020Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Prostate embryonic development, pubertal and adult growth, maintenance, and regeneration are regulated through androgen signaling-mediated mesenchymal-epithelial interactions. Specifically, the essential role of mesenchymal androgen signaling in the development of prostate epithelium has been observed for over 30 years. However, the identity of the mesenchymal cells responsible for this paracrine regulation and related mechanisms are still unknown. Here, we provide the first demonstration of an indispensable role of the androgen receptor (AR) in sonic hedgehog (SHH) responsive Gli1-expressing cells, in regulating prostate development, growth, and regeneration. Selective deletion of AR expression in Gli1-expressing cells during embryogenesis disrupts prostatic budding and impairs prostate development and formation. Tissue recombination assays showed that urogenital mesenchyme (UGM) containing AR-deficient mesenchymal Gli1-expressing cells combined with wildtype urogenital epithelium (UGE) failed to develop normal prostate tissue in the presence of androgens, revealing the decisive role of AR in mesenchymal SHH responsive cells in prostate development. Prepubescent deletion of AR expression in Gli1-expressing cells resulted in severe impairment of androgen-induced prostate growth and regeneration. RNA-sequencing analysis showed significant alterations in signaling pathways related to prostate development, stem cells, and organ morphogenesis in AR-deficient Gli1-expressing cells. Among these altered pathways, the transforming growth factor β1 (TGFβ1) pathway was up-regulated in AR-deficient Gli1-expressing cells. We further demonstrated the activation of TGFβ1 signaling in AR-deleted prostatic Gli1-expressing cells, which inhibits prostate epithelium growth through paracrine regulation. These data demonstrate a novel role of the AR in the Gli1-expressing cellular niche for regulating prostatic cell fate, morphogenesis, and renewal, and elucidate the mechanism by which mesenchymal androgen-signaling through SHH-responsive cells elicits the growth and regeneration of prostate epithelium.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.