Evidence map›Paper›PMID 36323713›Full record

ArticleNature communications2022

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

Alex Hiroto, Won Kyung Kim, Ariana Pineda, Yongfeng He, Dong-Hoon Lee, Vien Le, Adam W Olson, Joseph Aldahl, Christian H Nenninger, Alyssa J Buckley and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.1field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Alex Hiroto *Department of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Won Kyung Kim *Department of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Ariana PinedaDepartment of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Yongfeng HeDepartment of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Dong-Hoon LeeDepartment of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Vien LeDepartment of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Adam W OlsonDepartment of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Joseph AldahlDepartment of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Christian H NenningerDepartment of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Alyssa J BuckleyDepartment of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA.
Guang-Qian XiaoDepartment of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Joseph GeradtsDepartment of Pathology and Laboratory Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
Zijie SunDepartment of Cancer Biology, Cancer Center and Beckman Research Institute, City of Hope, Duarte, CA, USA. zjsun@coh.org.ORCID 0000-0002-6787-6272
City of Hope · USCity Of Hope National Medical Center · USEast Carolina University · USUniversity of Southern California · US

Funding

Roles of the androgen receptor and its co-regulators in prostate tumorigenesisR01CA070297 · NCI · STANFORD UNIVERSITY · PI SUN, ZIJIE · 2003 to 2025
$5.0M
DNA repair gene mutations and prostate cancerR01CA233664 · NCI · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI SHEN, BINGHUI, SUN, ZIJIE · 2020 to 2024
$3.4M
Wnt responsive stem cells in the prostateR01DK104941 · NIDDK · STANFORD UNIVERSITY · PI SUN, ZIJIE · 2015 to 2024
$3.0M
A New Mechanism for Castration Resistant Prostate CancerR01CA166894 · NCI · STANFORD UNIVERSITY · PI SUN, ZIJIE · 2015 to 2018
$1.2M
NCI NIH HHS R01 CA070297NCI NIH HHS R01 CA166894NCI NIH HHS R01 CA233664NIDDK NIH HHS R01 DK104941
6 · The paper itself

Abstract

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.

Indexed as

ProstateProstatic NeoplasmsAndrogensAnimalsCarcinogenesisEpithelial CellsHumansMaleMiceReceptors, AndrogenStromal CellsAndrogensReceptors, Androgen

Identifiers

PMID36323713
PMCPMC9630272
OpenAlexW4308147255

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.