Evidence map›Paper›PMID 41168397›Full record

ArticleNature genetics2025

Transcription factor switching drives subtype-specific pancreatic cancer.

Shalini V Rao, Lisa Young, Danya Cheeseman, Sean Flynn, Niklas Krebs, Dominique-Laurent Couturier, Stephanie Mack, Rebecca Brais, Jill Temple, Amy Smith and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature genetics, 2025. 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. The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026
    Review
  3. Article
  4. 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

32 authors.

Shalini V RaoCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Lisa YoungCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Danya CheesemanCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Sean FlynnDepartment of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
Niklas KrebsWest German Cancer Center, Experimental Urology, University Hospital Essen, Essen, Germany.
Dominique-Laurent CouturierCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-5774-5036
Stephanie MackCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Rebecca BraisCambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Jill TempleCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Amy SmithCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Evangelia PapachristouCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-5835-2055
Catarina PelicanoCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-7039-2922
Chandra Sekhar Reddy ChilamakuriCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Krzysztof HerkaCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Hideo BabaDepartment of Pathology, University Hospital Essen, Essen, Germany.
Luay FarahBridge Institute of Experimental Tumor Therapy (BIT) and Division of Solid Tumour Translational Oncology, German Cancer Consortium (DKTK), University Hospital Essen, Essen, Germany.
Phyllis F CheungBridge Institute of Experimental Tumor Therapy (BIT) and Division of Solid Tumour Translational Oncology, German Cancer Consortium (DKTK), University Hospital Essen, Essen, Germany.
Jens SivekeBridge Institute of Experimental Tumor Therapy (BIT) and Division of Solid Tumour Translational Oncology, German Cancer Consortium (DKTK), University Hospital Essen, Essen, Germany.
Stéphane GuerrierFaculty of Science, University of Geneva, Geneva, Switzerland.
Luca InsoliaFaculty of Science, University of Geneva, Geneva, Switzerland.ORCID http://orcid.org/0000-0003-4169-5446
Michael GillCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Emily Archer GoodeCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Steven KupczakCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Yi ChengCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Giacomo BorsariCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-0584-5737
Duncan JodrellCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-9360-1670
Clive D'SantosCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Alasdair RussellCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Barbara T GrünwaldWest German Cancer Center, Experimental Urology, University Hospital Essen, Essen, Germany.
Eva SerraoAddenbrooke's hospital, Cambridge, UK.
Igor ChernukhinCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Jason S CarrollCancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. jason.carroll@cruk.cam.ac.uk.ORCID http://orcid.org/0000-0003-3643-0080

Funding

Cancer Research UK (CRUK) G101107Pancreatic Cancer UK G109884
6 · The paper itself

Abstract

Emerging evidence suggests that lineage-specifying transcription factors control the progression of pancreatic ductal adenocarcinoma (PDAC). We have discovered a transcription factor switching mechanism involving the poorly characterized orphan nuclear receptor HNF4G and the putative pioneer factor FOXA1, which drives PDAC progression. Using our unbiased protein interactome discovery approach, we identified HNF4A and HNF4G as reproducible, FOXA1-associated proteins, in both preclinical models and Whipple surgical samples. In the primary tumor context, we consistently find that the dominant transcription factor is HNF4G, where it functions as the driver. A molecular switch occurs in advanced disease, whereby HNF4G expression or activity decreases, unmasking FOXA1's transcriptional potential. Derepressed FOXA1 drives late-stage disease by orchestrating metastasis-specific enhancer-promoter loops to regulate the expression of metastatic genes. Overall survival is influenced by HNF4G and FOXA1 activity in primary tumor growth and in metastasis, respectively. We suggest that the existence of stage-dependent transcription factor activity, triggered by molecular compartmentalization, mediates the progression of PDAC.

Indexed as

Carcinoma, Pancreatic DuctalHepatocyte Nuclear Factor 3-alphaHepatocyte Nuclear Factor 4Pancreatic NeoplasmsTranscription FactorsAnimalsCell Line, TumorDisease ProgressionGene Expression Regulation, NeoplasticHumansMiceFOXA1 protein, humanHepatocyte Nuclear Factor 3-alphaHepatocyte Nuclear Factor 4HNF4A protein, humanTranscription Factors

Identifiers

PMID41168397
PMCPMC12695649

What Socratic 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 Socratic graph.