Evidence map›Paper›PMID 39560993›Full record

ArticleThe Journal of clinical investigation2024

Low tristetraprolin expression activates phenotypic plasticity and primes transition to lethal prostate cancer in mice.

Katherine L Morel, Beatriz Germán, Anis A Hamid, Jagpreet S Nanda, Simon Linder, Andries M Bergman, Henk van der Poel, Ingrid Hofland, Elise M Bekers, Shana Y Trostel and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
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

23 authors.

Katherine L MorelSouth Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, South Australia, Australia.
Beatriz GermánCenter for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Anis A HamidDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Jagpreet S NandaDivision of Hematology and Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Simon LinderDivision of Oncogenomics, Oncode Institute.
Andries M BergmanDivision of Oncogenomics, Oncode Institute.
Henk van der PoelDivision of Urology.
Ingrid HoflandCore Facility Molecular Pathology and Biobanking; and.
Elise M BekersDivision of Pathology; Netherlands Cancer Institute, Amsterdam, Netherlands.
Shana Y TrostelGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Deborah L BurkhartDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
Scott WilkinsonGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Anson T KuGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Minhyung KimDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Jina KimDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Duanduan MaDavid H. Koch Institute for Integrative Cancer Research, Bioinformatics and Computing Facility of Swanson Biotechnology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Jasmine T PlummerDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Sungyong YouDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Xiaofeng A SuCenter for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
Wilbert ZwartDivision of Oncogenomics, Oncode Institute.
Adam G SowalskyGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Christopher J SweeneySouth Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, South Australia, Australia.
Leigh EllisCenter for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.

Funding

Exploiting RB1 deficiency for the treatment of lethal neuroendocrine prostate cancerR01CA207757 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI ELLIS, LEIGH, GOODRICH, DAVID W. · 2016 to 2020
$2.8M
ATR Dependency as a Novel Therapeutic Target in Lethal RB Deficient ProstateCancerR01CA252468 · NCI · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI Leigh Ellis · 2020 to 2026
$1.5M
Identifying EZH2-dependent vulnerabilities in RB deficient prostate cancerR21CA257484 · NCI · HENRY M. JACKSON FDN FOR THE ADV MIL/MED · PI ELLIS, LEIGH · 2021 to 2022
$425k
NCI NIH HHS R01 CA207757NCI NIH HHS R01 CA252468NCI NIH HHS R21 CA257484
6 · The paper itself

Abstract

Phenotypic plasticity is a hallmark of cancer and is increasingly realized as a mechanism of resistance to androgen receptor-targeted (AR-targeted) therapy. Now that many prostate cancer (PCa) patients are treated upfront with AR-targeted agents, it is critical to identify actionable mechanisms that drive phenotypic plasticity, to prevent the emergence of resistance. We showed that loss of tristetraprolin (TTP; gene ZFP36) increased NF-κB activation, and was associated with higher rates of aggressive disease and early recurrence in primary PCa. We also examined the clinical and biological impact of ZFP36 loss with co-loss of PTEN, a known driver of PCa. Analysis of multiple independent primary PCa cohorts demonstrated that PTEN and ZFP36 co-loss was associated with increased recurrence risk. Engineering prostate-specific Zfp36 deletion in vivo induced prostatic intraepithelial neoplasia, and, with Pten codeletion, resulted in rapid progression to castration-resistant adenocarcinoma. Zfp36 loss altered the cell state driven by Pten loss, as demonstrated by enrichment of epithelial-mesenchymal transition (EMT), inflammation, TNF-α/NF-κB, and IL-6-JAK/STAT3 gene sets. Additionally, our work revealed that ZFP36 loss also induced enrichment of multiple gene sets involved in mononuclear cell migration, chemotaxis, and proliferation. Use of the NF-κB inhibitor dimethylaminoparthenolide (DMAPT) induced marked therapeutic responses in tumors with PTEN and ZFP36 co-loss and reversed castration resistance.

Indexed as

Gene Expression Regulation, NeoplasticNeoplasm ProteinsProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantTristetraprolinAnimalsCell Line, TumorHumansMaleMiceMice, KnockoutNF-kappa BPTEN PhosphohydrolaseSTAT3 Transcription FactorNeoplasm ProteinsNF-kappa BPTEN PhosphohydrolasePTEN protein, humanPten protein, mouseSTAT3 Transcription FactorTristetraprolinZFP36 protein, humanZfp36 protein, mouseCell biologyMouse modelsOncologyProstate cancer

Identifiers

PMID39560993
PMCPMC11735106

What OpenQuestion holds

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Registered trials

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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.