Evidence map›Paper›PMID 42215676›Full record

ArticleCommunications biology2026

PU.1 is a mediator of the reactive stromal response associated with castration-resistant prostate cancer.

Francesco Bonollo, Daniel Hanhart, Simone de Brot, Wanli Cheng, Panagiotis Chouvardas, Beat Roth, George N Thalmann, Natalie Sampson, Marianna Kruithof-de Julio, Sofia Karkampouna

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

10 authors.

Francesco BonolloUrology Research Laboratory, Department for BioMedical Research, University of Bern, Bern, Switzerland.
Daniel HanhartUrology Research Laboratory, Department for BioMedical Research, University of Bern, Bern, Switzerland.ORCID http://orcid.org/0000-0003-0665-8607
Simone de BrotCOMPATH, Institute of Animal Pathology, University of Bern, Bern, Switzerland.
Wanli ChengUrology Research Laboratory, Department for BioMedical Research, University of Bern, Bern, Switzerland.
Panagiotis ChouvardasUrology Research Laboratory, Department for BioMedical Research, University of Bern, Bern, Switzerland.ORCID http://orcid.org/0000-0003-1527-3151
Beat RothDepartment of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
George N ThalmannDepartment of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Natalie SampsonDepartment of Urology, Medical University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0000-0001-9326-8177
Marianna Kruithof-de JulioUrology Research Laboratory, Department for BioMedical Research, University of Bern, Bern, Switzerland. marianna.kruithofdejulio@unibe.ch.ORCID http://orcid.org/0000-0002-6085-7706
Sofia KarkampounaUrology Research Laboratory, Department for BioMedical Research, University of Bern, Bern, Switzerland. sofia.karkampouna@unibe.ch.ORCID http://orcid.org/0000-0002-1716-5237

Funding

Novartis Stiftung für Medizinisch-Biologische Forschung (Novartis Foundation for Medical-Biological Research) #23B099Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 189149
6 · The paper itself

Abstract

Emerging evidence demonstrates the pivotal role played by the tumor microenvironment, particularly cancer-associated fibroblasts, during the development of castration-resistant prostate cancer. In this study, the molecular composition of the tumor microenvironment of androgen-sensitive and castration-resistant metastatic prostate cancer is investigated by utilizing patient-derived xenograft models. Transcriptomic and histological analysis identify the presence of a pro-fibrotic stroma in the castration-resistant (LAPC9) versus the castration-sensitive (PNPCa, BM18) models, characterized by high levels of collagen and tenascin C deposition and upregulation of inflammatory markers. Intra-tumoral collagen- and tenascin-positive stromal areas specifically correlate with higher tumor invasiveness. Master regulator analysis identifies the transcription factor PU.1 as a mediator of the LAPC9 pro-fibrotic phenotype, whose transcriptional activity can be specifically inhibited by the small molecule DB1976. To test the effect of pharmacologic PU.1 inhibition a novel organoid-fibroblast 3D co-culture system, able to mimic features of the in vivo tumor microenvironment, is established. Inhibition of stromal PU.1 activity reverts the pro-fibrotic phenotype and, in turn, reduces tumor organoid growth. Besides identifying a novel molecular player of the pro-fibrotic stromal phenotype in prostate cancer, this study highlights the applicability of 3D tumor organoid-fibroblast co-cultures as in vitro tools to test the effect of stromal-targeting compounds.

Indexed as

Prostatic Neoplasms, Castration-ResistantProto-Oncogene ProteinsStromal CellsTrans-ActivatorsTumor MicroenvironmentAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMaleMiceProto-Oncogene Protein Spi-1TenascinProto-Oncogene ProteinsProto-Oncogene Protein Spi-1TenascinTrans-Activators

Identifiers

PMID42215676
PMCPMC13547233

What OpenQuestion holds

Textmetadata
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.