Inflammation-induced NFATc1-STAT3 transcription complex promotes pancreatic cancer initiation by KrasG12D.
Cancer-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.


CONCLUSIONS
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.
Authors' 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.
Sandra
S
Baumgart
Authors' 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.
Nai-Ming
NM
Chen
Authors' 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
JT
Siveke
Authors' 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
Alexander
A
König
Authors' 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.
Jin-San
JS
Zhang
Authors' 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
SK
Singh
Authors' 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
E
Wolf
Authors' 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
M
Bartkuhn
Authors' 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
I
Esposito
Authors' 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.
Elisabeth
E
Heßmann
Authors' 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
J
Reinecke
Authors' 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
J
Nikorowitsch
Authors' 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
M
Brunner
Authors' 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
G
Singh
Authors' 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
ME
Fernandez-Zapico
Authors' 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
T
Smyrk
Authors' 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
WR
Bamlet
Authors' 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
M
Eilers
Authors' 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
A
Neesse
Authors' 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
TM
Gress
Authors' 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
DD
Billadeau
Authors' 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
D
Tuveson
Authors' 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.
Raul
R
Urrutia
Authors' 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
V
Ellenrieder
D000818:Animals; D045744:Cell Line, Tumor; D002108:Ceruletide; D015972:Gene Expression Regulation, Neoplastic; D008822:Mice, Transgenic; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D002108:Ceruletide; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)