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Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis.

Publication ,  Journal Article
Hiroto, A; Kim, WK; Pineda, A; He, Y; Lee, D-H; Le, V; Olson, AW; Aldahl, J; Nenninger, CH; Buckley, AJ; Xiao, G-Q; Geradts, J; Sun, Z
Published in: Nat Commun
November 2, 2022

The androgen receptor (AR)-signaling pathways are essential for prostate tumorigenesis. Although significant effort has been devoted to directly targeting AR-expressing tumor cells, these therapies failed in most prostate cancer patients. Here, we demonstrate that loss of AR in stromal sonic-hedgehog Gli1-lineage cells diminishes prostate epithelial oncogenesis and tumor development using in vivo assays and mouse models. Single-cell RNA sequencing and other analyses identified a robust increase of insulin-like growth factor (IGF) binding protein 3 expression in AR-deficient stroma through attenuation of AR suppression on Sp1-regulated transcription, which further inhibits IGF1-induced Wnt/β-catenin activation in adjacent basal epithelial cells and represses their oncogenic growth and tumor development. Epithelial organoids from stromal AR-deficient mice can regain IGF1-induced oncogenic growth. Loss of human prostate tumor basal cell signatures reveals in basal cells of stromal AR-deficient mice. These data demonstrate a distinct mechanism for prostate tumorigenesis and implicate co-targeting stromal and epithelial AR-signaling for prostate cancer.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 2, 2022

Volume

13

Issue

1

Start / End Page

6552

Location

England

Related Subject Headings

  • Stromal Cells
  • Receptors, Androgen
  • Prostatic Neoplasms
  • Prostate
  • Mice
  • Male
  • Humans
  • Epithelial Cells
  • Carcinogenesis
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
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Hiroto, A., Kim, W. K., Pineda, A., He, Y., Lee, D.-H., Le, V., … Sun, Z. (2022). Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis. Nat Commun, 13(1), 6552. https://doi.org/10.1038/s41467-022-34282-w
Hiroto, Alex, Won Kyung Kim, Ariana Pineda, Yongfeng He, Dong-Hoon Lee, Vien Le, Adam W. Olson, et al. “Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis.Nat Commun 13, no. 1 (November 2, 2022): 6552. https://doi.org/10.1038/s41467-022-34282-w.
Hiroto A, Kim WK, Pineda A, He Y, Lee D-H, Le V, et al. Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis. Nat Commun. 2022 Nov 2;13(1):6552.
Hiroto, Alex, et al. “Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis.Nat Commun, vol. 13, no. 1, Nov. 2022, p. 6552. Pubmed, doi:10.1038/s41467-022-34282-w.
Hiroto A, Kim WK, Pineda A, He Y, Lee D-H, Le V, Olson AW, Aldahl J, Nenninger CH, Buckley AJ, Xiao G-Q, Geradts J, Sun Z. Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis. Nat Commun. 2022 Nov 2;13(1):6552.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 2, 2022

Volume

13

Issue

1

Start / End Page

6552

Location

England

Related Subject Headings

  • Stromal Cells
  • Receptors, Androgen
  • Prostatic Neoplasms
  • Prostate
  • Mice
  • Male
  • Humans
  • Epithelial Cells
  • Carcinogenesis
  • Animals