ArticleNature cancer2025
Self-amplifying NRF2-EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer.
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In one paragraph
Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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.
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.
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Who cites it
7 citing papers in PubMed.
- Inhibition of Pax6 sumoylation suppresses the tumorigenicity of pancreatic cancer cells.Cell death and differentiation · 2026Article
- Potential oncogenic risks of Keap1-targeting PROTACs: Caution warranted in drug design.Acta pharmaceutica Sinica. B · 2026Article
- NADPH-producing enzymes restrict the formation of pancreatic precancerous lesions.Nature metabolism · 2026Article
- Metabolism modulates stress and neoplasia.Nature metabolism · 2026Article
- Precancerous microenvironment: A signalling perspective.Current opinion in cell biology · 2026Review
- Selective targeting of NRF2-high pancreatic ductal adenocarcinoma with an NQO1-activatable prodrug.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- EZH2 and MMP1 Overexpression in Colorectal Cancer: Correlation with Tumor Aggressiveness and Clinicopathologic Features.Iranian journal of pathology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
42 authors.
Laura AntonucciLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Na LiDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, China.
Angeles DuranDepartment of Pathology and Laboratory Medicine and Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0001-9576-0587
Isidoro CoboDepartment of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Chiara NicolettiDevelopment, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-0872-6506
Kosuke WatariLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California, San Diego School of Medicine, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0260-2323
Shuvro Prokash NandiDepartment of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4855-4697
Feng ZhuCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Yongmei ZhaoCCR Sequencing Facility Bioinformatics Group, Bioinformatics and Computational Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.ORCID http://orcid.org/0000-0003-0800-4658
Irene RiahiDepartments of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
Motoyuki TsudaDepartment of Molecular and Medical Genetics, School of Medicine Oregon Health and Science University, Portland, OR, USA.
Vidhi M ShahDepartment of Molecular and Medical Genetics, School of Medicine Oregon Health and Science University, Portland, OR, USA.
Terry MorganDepartment of Pathology, School of Medicine Oregon Health and Science University, Portland, OR, USA.
Trent WaughBrenden-Colson Center for Pancreatic Care, School of Medicine Oregon Health and Science University, Portland, OR, USA.
Luca CaputoDevelopment, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-1697-9968
Yuan LiuLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Alexandra Rundberg NilssonLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California, San Diego School of Medicine, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-7492-4164
Hongxu XianLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Jelena TodoricLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Li GuLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California, San Diego School of Medicine, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5812-9024
Elsa Sanchez-LopezDepartment of Orthopedic Surgery, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Guido EiblDepartment of Surgery, University of California, Los Angeles, Los Angeles, CA, USA.
Emily A VucicDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA.
Michal KrawczykDepartment of Physiology and Biophysics, Center for Translational Vision Research, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Qianlan XuDepartment of Physiology and Biophysics, Center for Translational Vision Research, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Andrew M LowyDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Georgia HatzivassiliouGenentech, Inc., San Francisco, CA, USA.
Merone Roose-GirmaGenentech, Inc., San Francisco, CA, USA.
Dorota Skowronska-KrawczykDepartment of Physiology and Biophysics, Center for Translational Vision Research, School of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-5758-4225
David A ScottCancer Metabolism Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-8668-2449
Dafna Bar-SagiDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA.
Pablo TamayoCenter for Novel Therapeutics and Division of Medical Genetics, Department of Medicine, Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Ying WuCCR Sequencing Facility Bioinformatics Group, Bioinformatics and Computational Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Rosalie C SearsDepartment of Molecular and Medical Genetics, School of Medicine Oregon Health and Science University, Portland, OR, USA.ORCID http://orcid.org/0000-0003-1558-2413
Christopher K GlassDepartment of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.
Ludmil B AlexandrovDepartment of Cellular & Molecular Medicine, University of California, San Diego School of Medicine, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-3596-4515
Pier Lorenzo PuriDevelopment, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
David W DawsonDepartments of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
Yinling HuCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.ORCID http://orcid.org/0000-0002-4795-8537
Maria T Diaz-MecoDepartment of Pathology and Laboratory Medicine and Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-0147-0998
Jorge MoscatDepartment of Pathology and Laboratory Medicine and Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-9442-3834
Michael KarinLaboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California, San Diego School of Medicine, La Jolla, CA, USA. karinoffice@health.ucsd.edu.ORCID http://orcid.org/0000-0002-2758-6473
Funding
VIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9MTumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4MFunctions of IKK&945; in Skin Homeostasis and Skin TumorigenesisZIABC011212 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HU, YINLING · 2009 to 2025
$11.0MSan Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Bernd G. Schnabl · 2019 to 2026
$10.8MRole of hypernutrition and metabolic stress in non-alcoholic steatohepatitis (NASH) driven hepatocellular carcinoma (HCC)P01CA281819 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Pablo Tamayo · 2024 to 2026
$9.2MRole of IKK alpha in lung squamous cell carcinoma developmentZIABC011391 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HU, YINLING · 2011 to 2025
$9.1MOncogenic Ras-induced macropinocytosis: A new paradigm for metabolic adaptationR35CA210263 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BAR-SAGI, DAFNA · 2016 to 2022
$6.6MNF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of InflammationR37AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin · 2018 to 2026
$6.0MProject 3: Role of the pancreatic fibroinflammatory microenvironment in obesity-promoted pancreatic cancerP01CA236585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GO, VAY LIANG W · 2020 to 2024
$5.6MThe effect of cancer cell produced collagen 1 homotrimers on DDR1 signaling activation by microenvironmental collagen 1 fragments.U01CA274295 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin, ANDREW M LOWY · 2022 to 2026
$5.2MA Rational Systematic Approach to Find Combinations of Pharmacologic and Immune Therapies that Target Identifiable Oncogenic StatesU01CA217885 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COHEN, EZRA, KAUFMAN, DAN S. · 2017 to 2021
$5.1MIntramural NIH HHS ZIA BC011212Intramural NIH HHS ZIA BC011391NCI NIH HHS P01 CA236585NCI NIH HHS P01 CA281819NCI NIH HHS P30 CA023100NCI NIH HHS P30 CA030199NCI NIH HHS R01 CA118165NCI NIH HHS R01 CA155620NCI NIH HHS R01 CA186241NCI NIH HHS R01 CA211794NCI NIH HHS R01 CA246765NCI NIH HHS R01 CA250025NCI NIH HHS R01 CA265892NCI NIH HHS R01 CA269919NCI NIH HHS R01 CA275846NCI NIH HHS R01 CA285997NCI NIH HHS R03 CA223717NCI NIH HHS R21 CA274265NCI NIH HHS R35 CA210263NCI NIH HHS R50 CA265332NCI NIH HHS R50 CA283813NCI NIH HHS U01 CA217885NCI NIH HHS U01 CA224012NCI NIH HHS U01 CA274295NCI NIH HHS U24 CA295532NEI NIH HHS R01 EY027011NIAID NIH HHS R25 AI147376NIAID NIH HHS R37 AI043477NIAMS NIH HHS K01 AR077111NIDDK NIH HHS P30 DK063491NIDDK NIH HHS P30 DK120515NIEHS NIH HHS R01 ES030993NIEHS NIH HHS R01 ES032547NIGMS NIH HHS R01 GM134712
Abstract
Pancreatic ductal adenocarcinoma (PDAC) emerges from mutant KRAS-harboring but dormant low-grade pancreatic intraepithelial neoplasia (PanIN). To examine the role of oxidative stress, a putative PDAC risk factor, we established an organoid-based transformation system. Although the prototypic oxidant H
Indexed as
Carcinoma, Pancreatic DuctalCell Transformation, NeoplasticEnhancer of Zeste Homolog 2 ProteinEpigenesis, GeneticNF-E2-Related Factor 2Pancreatic NeoplasmsProto-Oncogene Proteins p21(ras)AnimalsCarcinoma in SituCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceNeoplasm InvasivenessOrganoidsOxidative StressEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanEzh2 protein, mouseKRAS protein, humanNFE2L2 protein, humanNfe2l2 protein, mouseNF-E2-Related Factor 2Proto-Oncogene Proteins p21(ras)
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