ArticleCell reports2020
HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer.
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Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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95citing papers in PubMed
6.7field-weighted citation impact, top 2% of its field
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Who cites it
95 citing papers in PubMed, 124 citations in OpenAlex.
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- DHX33 inhibitors induced transcriptional changes for a subset of genes in cancer cells.Scientific reports · 2026Article
- GLIS3 marks a neural-like progenitor cell state that drives metastasis in pancreatic ductal adenocarcinoma.Cell reports · 2026Article
- The role of HNF4α in adenocarcinoma.Biochemical Society transactions · 2026Review
- Exploring and experimental validation of SLC7A11 and ferroptosis related prognostic genes in non-small cell lung cancer using bulk RNA sequencing and single-cell RNA sequencing.Biology direct · 2026Article
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- Clonal evolutionary analysis reveals patterns of malignant transformation of Intraductal Papillary Mucinous Neoplasms of the pancreas.Nature communications · 2026Article
- Epigenetic and transcriptional control of classical and basal-like cell states in pancreatic ductal adenocarcinoma.Gastroenterology report · 2026Review
- Mutant p53 regulates reversible subtype plasticity in pancreatic cancer.Cellular and molecular life sciences : CMLS · 2025Article
- Transcription factor switching drives subtype-specific pancreatic cancer.Nature genetics · 2025Article
- Differential Control of Growth and Identity by HNF4α Isoforms in Pancreatic Ductal Adenocarcinoma.Molecular cancer research : MCR · 2025Article
- Methods and Guidelines for Metabolism Studies: Applications to Cancer Research.International journal of molecular sciences · 2025Review
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- Analysis of an engineered organoid model of pancreatic cancer identifies hypoxia as a contributing factor in determining transcriptional subtypes.Scientific reports · 2025Article
- The landscape of malignant transition: Unraveling cancer cell-of-origin and heterogeneous tissue microenvironment.Cancer letters · 2025Article
- Molecular mechanisms altering cell identity in cancer.Oncogene · 2025Review
- Improving outcomes of patients with pancreatic cancer.Nature reviews. Clinical oncology · 2025Review
- Emerging Tumor Biomarkers in Pancreatic Cancer and Their Clinical Implications.Current issues in molecular biology · 2025Review
- Sialic acid metabolism-based classification reveals novel metabolic subtypes with distinct characteristics of tumor microenvironment and clinical outcomes in gastric cancer.Cancer cell international · 2025Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
46 authors at 19 institutions in 5 countries.
Holly BruntonInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Giuseppina CaligiuriInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland.
Richard CunninghamInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland.
Rosie Upstill-GoddardInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland.
Ulla-Maja BaileyInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Ian M GarnerEpigenetics Unit, Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Craig NourseCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Stephan DreyerInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK.
Marc JonesStratified Medicine Scotland Innovation Centre, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK.
Kim Moran-JonesStratified Medicine Scotland Innovation Centre, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK.
Derek W WrightInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland.
Viola Paulus-HockCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Colin NixonCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Gemma ThomsonCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Nigel B JamiesonInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK.
Grant A McGregorCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Lisa EversInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland.
Colin J McKayInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK.
Aditi GulatiCRUK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Rachel BroughCRUK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Ilirjana BajramiCRUK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Stephen J PettittCRUK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Michele L DziubinskiDepartment of Molecular and Integrative Physiology, University of Michigan, 4304 Rogel Cancer Center Drive, Ann Arbor, MI 48109, USA.
Simon T BarryBioscience, Oncology, IMED Biotech Unit, AstraZeneca, Cambridge, UK.
Robert GrützmannDepartment of Surgery, Universitätsklinikum Erlangen, Erlangen, Germany.
Robert BrownEpigenetics Unit, Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Edward CurryEpigenetics Unit, Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Glasgow Precision Oncology Laboratory
Australian Pancreatic Cancer Genome Initiative
Marina PajicThe Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst and Garvan Institute of Medical Research, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Elizabeth A MusgroveInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland.
Gloria M PetersenMayo Clinic, Rochester, MN 55905, USA.
Emma ShanksCancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Alan AshworthCRUK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94158, USA.
Howard C CrawfordDepartment of Molecular and Integrative Physiology, University of Michigan, 4304 Rogel Cancer Center Drive, Ann Arbor, MI 48109, USA.
Diane M SimeonePancreatic Cancer Center, Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, USA.
Fieke E M FroelingEpigenetics Unit, Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
Christopher J LordCRUK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
Debabrata MukhopadhyayDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Jacksonville, FL 32224, USA.
Christian PilarskyDepartment of Surgery, Universitätsklinikum Erlangen, Erlangen, Germany.
Sean E GrimmondUniversity of Melbourne Centre for Cancer Research, University of Melbourne, Melbourne 3010, VIC, Australia.
Jennifer P MortonInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
Owen J SansomInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
David K ChangInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia.
Peter J BaileyInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK; Department of General Surgery, University of Heidelberg, Heidelberg 69120, Germany. Electronic address: peter.bailey.2@glasgow.ac.uk.
Andrew V BiankinInstitute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, Scotland; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow G31 2ER, UK; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia. Electronic address: andrew.biankin@glasgow.ac.uk.
Glasgow Royal Infirmary · GBCancer Research UK · GBInstitute of Cancer Research · GBUniversity of Glasgow · GBUniversitätsklinikum Erlangen · DEGarvan Institute of Medical Research · AUHeidelberg University · DEUniversity of Michigan · USImperial College London · GBQueen Elizabeth University Hospital · GBThe University of Melbourne · AUCold Spring Harbor Laboratory · USJacksonville College · USMayo Clinic in Arizona · USNYU Langone Health · USAstraZeneca (United Kingdom) · GBBreast Cancer Now · GBCancer Research UK Scotland Institute · GBMRC University of Glasgow Centre for Virus Research · GB
Funding
Tumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI KLEIN, ALISON P · 1993 to 2022
$54.6MTissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI MUKHOPADHYAY, DEBABRATA · 2004 to 2018
$32.7MTargeting Pancreatic Cancer Using Peptide Chemistry: From Bench to BedsideR01CA150190 · NCI · MAYO CLINIC ROCHESTER · PI MIERKE, DALE F, MUKHOPADHYAY, DEBABRATA · 2010 to 2021
$5.7MInterrupting Cellular Crosstalk in the Immunosuppressive Microenvironment of Pancreas CancerU01CA224145 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CRAWFORD, HOWARD C., PASCA DI MAGLIANO, MARINA · 2017 to 2021
$2.6MMetaplastic Tuft Cells in Pancreatic CancerR01CA247516 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CRAWFORD, HOWARD C. · 2020 to 2024
$2.3MRole of Vav1 protooncogene in pancreatic cancerP20CA102701 · NCI · MAYO CLINIC COLL OF MEDICINE, ROCHESTER · PI PETERSEN, GLORIA M. · 2003 to 2003
$1.5MCancer Research UK 14276Cancer Research UK 21139Cancer Research UK 24439Cancer Research UK 25813Cancer Research UK 29996Cancer Research UK A14276Cancer Research UK A23526Cancer Research UK A25233Cancer Research UK A29996Cancer Research UK C29717/A17263Cancer Research UK C29717/A18484Cancer Research UK C596/A18076Cancer Research UK C596/A20921Medical Research CouncilNCI NIH HHS P20 CA102701NCI NIH HHS P50 CA062924NCI NIH HHS P50 CA102701NCI NIH HHS R01 CA150190NCI NIH HHS R01 CA247516NCI NIH HHS U01 CA224145Wellcome TrustWellcome Trust 103721/Z/14/Z
Abstract
Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3β inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC.
Indexed as
AdenocarcinomaBiomarkers, TumorCarcinoma, Pancreatic DuctalCell Line, TumorGATA6 Transcription FactorHepatocyte Nuclear Factor 4HumansBiomarkers, TumorGATA6 protein, humanGATA6 Transcription FactorHepatocyte Nuclear Factor 4HNF4A protein, humanchromatin landscapesGATA6GSK3BHNF4Aintronic and distal promotersmetabolic targetingPDAC subtypestherapeutic tolerance
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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.