Evidence map›Paper›PMID 41028981›Full record

ArticleCancer medicine2025

Detection of Genome-Wide IGF-1R Recruitment to Enhancer and Promoter Regions of Chromatin in Clinical Prostate Cancers.

Jack V Mills, Avigail Taylor, Reema Singh, Jinseon Kim, Simon Engledow, Richard Colling, Clare Verrill, Ian G Mills, Valentine M Macaulay

Abstract read
In one paragraph

Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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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. 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

9 authors.

Jack V MillsNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.ORCID https://orcid.org/0000-0002-1852-4596
Avigail TaylorNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Reema SinghNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Jinseon KimNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Simon EngledowWellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Richard CollingDepartment of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Clare VerrillNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Ian G MillsNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Valentine M MacaulayNuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Funding

Cancer Research UK C476/A27060Cancer Research UK CRUKDF-0221-VMIMJMMedical Research Council 1718_MSD_1113081NIHR CRN Thames Valley NetworkNIHR Oxford Biomedical Research CentreOxford CRUK Cancer CentreProstate Cancer UK RIA-ST2-024University of OxfordWellcome Trust 203141/A/16/Z
6 · The paper itself

Abstract

introductionNuclear insulin-like growth factor-1 receptor (IGF-1R) undergoes IGF-induced recruitment to cancer cell chromatin in vitro and associates with advanced prostate cancer (PCa) stage in clinical tissue, prompting this investigation of IGF-1R chromatin recruitment in vivo.

methodsHuman tissues surplus to diagnostic need were obtained from consenting patients undergoing transurethral resection of the prostate (TURP) or radical prostatectomy (RP). Initial tissue samples were processed for H3K4me1-positive control ChIP to optimise homogenisation, fixation and ChIP conditions. Following successful method optimization, IGF-1R and H3K4me1 ChIP-seq was performed on six treatment-naïve localized PCa samples, along with parallel IGF-1R immunohistochemistry analysis. MACS2 and LanceOtron peak callers were used to identify binding sites from ChIP-seq data and MEME Suite was used to identify an IGF-1R binding motif. In vitro chromatin immunoprecipitation qPCR (ChIP-qPCR) was used for ChIP-seq data validation.

resultsWe identified 5743 unique IGF-1R binding sites, with 37% within 3 kb of gene transcription start sites (TSSs). Of these sites, 72.3% coincided with enhancer mark H3K4me1, suggesting regulatory function. Motif analysis identified an IGF-1R consensus binding motif for the first time, with a sequence resembling that of the insulin receptor and PITX2 transcription factor binding motifs, supporting functional similarities. In vitro ChIP-qPCR confirmed IGF-1R recruitment to a site identified in vivo in the RRM2 TSS, a gene involved in DNA replication and repair and regulated by the IGF-axis, highlighting potential regulatory function of nuclear IGF-1R.

conclusionOverall, these data represent the first characterization of genome-wide IGF-1R recruitment in PCa tissue and are consistent with a transcriptional regulatory role, further elucidating the contribution of nuclear IGF-1R to advanced clinical stage.

Indexed as

ChromatinEnhancer Elements, GeneticPromoter Regions, GeneticProstatic NeoplasmsReceptor, IGF Type 1Binding SitesChromatin Immunoprecipitation SequencingGene Expression Regulation, NeoplasticHistonesHumansMaleProtein BindingChromatinHistonesIGF1R protein, humanReceptor, IGF Type 1ChIP‐seqenhancerIGF‐1Rpromoterprostate cancer

Identifiers

PMID41028981
PMCPMC12483945

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