ArticleCancer discovery2014
Inflammation-induced NFATc1-STAT3 transcription complex promotes pancreatic cancer initiation by KrasG12D.
Open access · greenAbstract read
In one paragraph
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
5.6field-weighted citation impact, top 3% of its field
What it found
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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
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Research trends and knowledge structure of pancreatic cancer and type 2 diabetes mellitus research: a two-decade CiteSpace analysis.Frontiers in endocrinology · 2026Pooled it
- Two Faces of NFAT Transcription Factors in LymphocytesBiomolecules · 2026Review
- Identification and characterization of a TGF-β-independent SMAD4-NFATc1-STAT3 regulatory axis.Journal of molecular cell biology · 2026Article
- MRPS16 Regulates NFATC2 Through the Wnt/β-Catenin Pathway to Promote Glioma Proliferation.Journal of cellular and molecular medicine · 2026Article
- Synergistic roles of NFATc1 and c-Jun in immunomodulation.Biochemistry and biophysics reports · 2025Review
- Single cell transcriptomics in a treatment-segregated cohort exposes a STAT3-regulated therapeutic gap in idiopathic pulmonary fibrosis.bioRxiv : the preprint server for biology · 2025Article
- EZH2 deletion does not affect acinar regeneration but restricts progression to pancreatic cancer in mice.JCI insight · 2024Article
- Advances in delivery systems for CRISPR/Cas-mediated cancer treatment: a focus on viral vectors and extracellular vesicles.Frontiers in immunology · 2024Review
- Role of CELF2 in ferroptosis: Potential targets for cancer therapy (Review).International journal of molecular medicine · 2023Review
- ETV6 represses inflammatory response genes and regulates HSPC function during stress hematopoiesis in mice.Blood advances · 2023Article
- A hybrid nanopharmaceutical for specific-amplifying oxidative stress to initiate a cascade of catalytic therapy for pancreatic cancer.Journal of nanobiotechnology · 2023Article
- Delayed and limited administration of the JAKinib tofacitinib mitigates chronic DSS-induced colitis.Frontiers in immunology · 2023Article
- Proliferation, apoptosis and invasion of human lung cancer cells are associated with NFATc1.Experimental and therapeutic medicine · 2023Article
- New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment.International journal of molecular sciences · 2022Review
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- Axon guidance receptor ROBO3 modulates subtype identity and prognosis via AXL-associated inflammatory network in pancreatic cancer.JCI insight · 2022Article
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- Salt-inducible kinase 3 protects tumor cells from cytotoxic T-cell attack by promoting TNF-induced NF-κB activation.Journal for immunotherapy of cancer · 2022Article
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- Calcium signaling induces a partial EMT.EMBO reports · 2021Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 5 institutions in 2 countries.
Sandra BaumgartAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Nai-Ming ChenAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New YorkAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Jens T SivekeAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Alexander KönigAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New YorkAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New YorkAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg
Jin-San ZhangAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Shiv K SinghAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Elmar WolfAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Marek BartkuhnAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Irene EspositoAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Elisabeth HeßmannAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New YorkAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Johanna ReineckeAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New YorkAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Julius NikorowitschAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Marius BrunnerAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Garima SinghAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Martin E Fernandez-ZapicoAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Thomas SmyrkAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
William R BamletAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Martin EilersAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Albrecht NeesseAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Thomas M GressAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Daniel D BilladeauAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
David TuvesonAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
Raul UrrutiaAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York urrutia.raul@mayo.edu ellenrie@med.uni-marburg.de.
Volker EllenriederAuthors' Affiliations:Signaling and Transcription Laboratory, Department of Gastroenterology, Philipps University, Marburg; Department of Gastroenterology and Gastrointestinal Oncology, University Medical Center Göttingen, Göttingen; II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität; Institute of Pathology, Helmholtz Zentrum, Munich; Theodor Boveri Institute, University of Würzburg, Würzburg; Institute for Genetics, Justus-Liebig-University, Giessen, Germany; Schulze Center for Novel Therapeutics, Division of Oncology Research; Divisions of Anatomic Pathology and Biostatistics, College of Medicine; Laboratory of Epigenetics and Chromatin Dynamics, Department of Medicine, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota; Barrow Brain Tumor Research Center, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York urrutia.raul@mayo.edu ellenrie@med.uni-marburg.de.
Cold Spring Harbor Laboratory · USUniversitätsmedizin Göttingen · DEKlinikum rechts der Isar · DEUniversity of Würzburg · DEUniversity of Giessen · DE
Funding
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3MTissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI MUKHOPADHYAY, DEBABRATA · 2004 to 2018
$32.7MPILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI Nicholas F. LaRusso · 2009 to 2026
$22.2MZINC FINGER GENES AND PANCREATIC CELL GROWTHR01DK052913 · NIDDK · MEDICAL COLLEGE OF WISCONSIN · PI LOMBERK, GWEN, URRUTIA, RAUL A. · 1998 to 2023
$7.0MNovel regulatory mechanisms of the osteoclast transcriptional programK08AR054859 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI ALIPRANTIS, ANTONIOS O · 2008 to 2012
$655kThe Role of Zinc Finger Genes in Pancreatic Cell GrowthR56DK052913 · NIDDK · MAYO CLINIC ROCHESTER · PI URRUTIA, RAUL A. · 2008 to 2008
$291kNCI NIH HHS P30 CA015083NCI NIH HHS P50 CA102701NIAMS NIH HHS K08 AR054859NIDDK NIH HHS DK52913NIDDK NIH HHS P30 DK084567NIDDK NIH HHS P30DK084567NIDDK NIH HHS R01 DK052913NIDDK NIH HHS R56 DK052913
Abstract
unlabelledCancer-associated inflammation is a molecular key feature in pancreatic ductal adenocarcinoma. Oncogenic KRAS in conjunction with persistent inflammation is known to accelerate carcinogenesis, although the underlying mechanisms remain poorly understood. Here, we outline a novel pathway whereby the transcription factors NFATc1 and STAT3 cooperate in pancreatic epithelial cells to promote Kras(G12D)-driven carcinogenesis. NFATc1 activation is induced by inflammation and itself accelerates inflammation-induced carcinogenesis in Kras(G12D) mice, whereas genetic or pharmacologic ablation of NFATc1 attenuates this effect. Mechanistically, NFATc1 complexes with STAT3 for enhancer-promoter communications at jointly regulated genes involved in oncogenesis, for example, Cyclin, EGFR and WNT family members. The NFATc1-STAT3 cooperativity is operative in pancreatitis-mediated carcinogenesis as well as in established human pancreatic cancer. Together, these studies unravel new mechanisms of inflammatory-driven pancreatic carcinogenesis and suggest beneficial effects of chemopreventive strategies using drugs that are currently available for targeting these factors in clinical trials. SIGNIFICANCE: Our study points to the existence of an oncogenic NFATc1-STAT3 cooperativity that mechanistically links inflammation with pancreatic cancer initiation and progression. Because NFATc1-STAT3 nucleoprotein complexes control the expression of gene networks at the intersection of inflammation and cancer, our study has significant relevance for potentially managing pancreatic cancer and other inflammatory-driven malignancies.
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AnimalsCell Line, TumorCeruletideGene Expression Regulation, NeoplasticMice, TransgenicNFATC Transcription FactorsPancreatic NeoplasmsPancreatitisProto-Oncogene Proteins p21(ras)STAT3 Transcription FactorCeruletideHras protein, mouseNfatc1 protein, mouseNFATC Transcription FactorsProto-Oncogene Proteins p21(ras)Stat3 protein, mouseSTAT3 Transcription Factor
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