Evidence map›Paper›PMID 38453924›Full record

ArticleNature communications2024

CRISPR/Cas9 model of prostate cancer identifies Kmt2c deficiency as a metastatic driver by Odam/Cabs1 gene cluster expression.

Huiqiang Cai, Bin Zhang, Johanne Ahrenfeldt, Justin V Joseph, Maria Riedel, Zongliang Gao, Sofie K Thomsen, Ditte S Christensen, Rasmus O Bak, Henrik Hager and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. 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

14 authors at 3 institutions in 2 countries.

Huiqiang CaiDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Bin ZhangComputational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.ORCID 0000-0001-8835-8370
Johanne AhrenfeldtDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Justin V JosephDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Maria RiedelDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Zongliang GaoDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Sofie K ThomsenDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Ditte S ChristensenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Rasmus O BakDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0002-7383-0297
Henrik HagerDepartment of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Mikkel H VendelboDepartment of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark.
Xin GaoComputational Bioscience Research Center, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.ORCID 0000-0002-7108-3574
Nicolai BirkbakDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0003-1613-9587
Martin K ThomsenDepartment of Biomedicine, Aarhus University, Aarhus, Denmark. mkt@biomed.au.dk.ORCID 0000-0002-5055-7531
Aarhus University · DKAarhus University Hospital · DKKing Abdullah University of Science and Technology · SA

Funding

Aarhus Universitets Forskningsfond (Aarhus University Research Foundation) AUFF-E-2015-FLS-9-8Aarhus Universitets Forskningsfond (Aarhus University Research Foundation) AUFF-E-2018-7-14Kræftens Bekæmpelse (Danish Cancer Society) R146-A9394Kræftens Bekæmpelse (Danish Cancer Society) R204-A12490Lundbeckfonden (Lundbeck Foundation) R272-2017-4040Novo Nordisk Fonden (Novo Nordisk Foundation) NNF21OC0071483
6 · The paper itself

Abstract

Metastatic prostate cancer (PCa) poses a significant therapeutic challenge with high mortality rates. Utilizing CRISPR-Cas9 in vivo, we target five potential tumor suppressor genes (Pten, Trp53, Rb1, Stk11, and RnaseL) in the mouse prostate, reaching humane endpoint after eight weeks without metastasis. By further depleting three epigenetic factors (Kmt2c, Kmt2d, and Zbtb16), lung metastases are present in all mice. While whole genome sequencing reveals few mutations in coding sequence, RNA sequencing shows significant dysregulation, especially in a conserved genomic region at chr5qE1 regulated by KMT2C. Depleting Odam and Cabs1 in this region prevents metastasis. Notably, the gene expression signatures, resulting from our study, predict progression-free and overall survival and distinguish primary and metastatic human prostate cancer. This study emphasizes positive genetic interactions between classical tumor suppressor genes and epigenetic modulators in metastatic PCa progression, offering insights into potential treatments.

Indexed as

CRISPR-Cas SystemsProstatic NeoplasmsAnimalsHumansMaleMiceMultigene FamilyTranscriptome

Identifiers

PMID38453924
PMCPMC10920892
OpenAlexW4392550041

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.