ArticleCell2020
Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma.
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Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
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91citing papers in PubMed, 1 pooled it
12.8field-weighted citation impact, top 1% of its field
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Diet-Induced Phospholipid Remodeling Dictates Ferroptosis Sensitivity and Tumorigenesis in the Pancreas.Cancer discovery · 2026Article
- Article
- Acinar-ductal metaplasia in pancreatitis and pancreatic ductal adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Variable efficacy of the non-covalent KRASNPJ precision oncology · 2026Article
- Workload-induced changes to cell state contribute to β-cell failure in diabetes.bioRxiv : the preprint server for biology · 2026Article
- Spatial Multiomics Analyses Reveal That Diabetes Promotes Pancreatic Cancer Progression by Stimulating Cholesterol-Induced Neutrophil Extracellular Trap Formation.Cancer research · 2026Article
- Persistent Global Associations Between Gallbladder-Biliary Diseases and Pancreatic Cancer: Evidence from 204 Countries and Territories Over 32 years.Digestive diseases and sciences · 2026Article
- Review
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development.Nature communications · 2026Article
- Rethinking the microenvironment's role in chemical-induced malignancy.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- Obesity and Cancer: Mechanisms, Epidemiological Evidence, and Potential Risk Reduction.Journal of obesity & metabolic syndrome · 2026Review
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Obesity enhances ovarian cancer chemotherapy efficacy through C1q-mediated tumor targeting and immune activation.Journal of nanobiotechnology · 2025Article
- Unraveling the glyco-immunity nexus in pancreatic cancer.Molecular cancer · 2025Review
- Normalizing Body Weight with a Dietary Strategy Mitigates Obesity-Accelerated Pancreatic Carcinogenesis in Mice.The Journal of nutrition · 2025Article
- Direct genetic transformation bypasses tumor-associated DNA methylation alterations.Genome biology · 2025Article
- Obesity and Pancreatic Diseases: From Inflammation to Oncogenesis and the Impact of Weight Loss Interventions.Nutrients · 2025Review
- Review
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors at 14 institutions in 2 countries.
Katherine Minjee ChungKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
Jaffarguriqbal SinghDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA.
Lauren LawresDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA.
Kimberly Judith DoransKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
Cathy GarciaDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA.
Daniel B BurkhardtDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Rebecca RobbinsKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
Arjun BhutkarKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA.
Rebecca CardoneDepartments of Internal Medicine and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Xiaojian ZhaoDepartments of Internal Medicine and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Ana BabicDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA.
Sara A VayrynenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA.
Andressa Dias CostaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA.
Jonathan A NowakDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Daniel T ChangDepartment of Radiation Oncology, Stanford Cancer Institute, Stanford, CA 94305, USA.
Richard F DunneDivision of Hematology and Oncology, Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14627, USA.
Aram F HezelDivision of Hematology and Oncology, Department of Medicine, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14627, USA.
Albert C KoongDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Joshua J WilhelmSchulze Diabetes Institute and Department of Surgery, University of Minnesota Medical Center, Minneapolis, MN 55454, USA.
Melena D BellinSchulze Diabetes Institute and Department of Surgery, University of Minnesota Medical Center, Minneapolis, MN 55454, USA; Department of Pediatrics, University of Minnesota Medical Center, Minneapolis, MN 55454, USA.
Vibe NylanderWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
Anna L GloynWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford OX3 7LE, UK.
Mark I McCarthyWellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford OX3 7LE, UK.
Richard G KibbeyDepartments of Internal Medicine and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Smita KrishnaswamyDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA.
Tyler JacksKoch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Charles S FuchsYale Cancer Center, Smilow Cancer Hospital, New Haven, CT 06511, USA.
Mandar Deepak MuzumdarDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Cancer Biology Institute, Yale University, West Haven, CT 06516, USA; Yale Cancer Center, Smilow Cancer Hospital, New Haven, CT 06511, USA. Electronic address: mandar.muzumdar@yale.edu.
Yale University · USHarvard University · USKoch Institute for Integrative Cancer Research At MITCentre for Human Genetics · GBUniversity of Minnesota Medical Center · USUniversity of Rochester Medical Center · USYale Cancer Center · USAllen Institute · USDana-Farber Cancer Institute · USMassachusetts Institute of Technology · USSmilow Cancer Hospital · USStanford Cancer InstituteThe University of Texas MD Anderson Cancer Center · USUniversity of Oxford · GB
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Kathrin Milbury · 1985 to 2026
$290.8MYale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MVIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Andreea O'Connell · 1985 to 2026
$93.9MYale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI BARBARA BURTNESS · 1985 to 2026
$85.0MSystems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI Steven H. Kleinstein · 2010 to 2026
$50.4MYale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Kevan C Herold, GERALD I SHULMAN · 1993 to 2026
$44.0MUSE OF RETROVIRUS PROMOTER TRAP VECTORS TO IDENTIFY ONCOGENES AND ANTI-ONCOGENESP01CA042063 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SHARP, PHILLIP A · 1986 to 2021
$30.5MPREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007499 · NIGMS · YALE UNIVERSITY · PI CARLSON, JOHN R, REINKE, VALERIE J · 1985 to 2022
$13.9MCirculating Biomarker Consortium for Pancreatic Cancer Early DetectionU01CA210171 · NCI · DANA-FARBER CANCER INST · PI Michael H. Rosenthal, Brian Matthew Wolpin · 2016 to 2026
$8.7MInstitutional Career Development CoreKL2TR001999 · NCATS · UNIVERSITY OF ROCHESTER · PI XIAO, JIN · 2016 to 2024
$5.2MIdentifying variants causal for Type 2 Diabetes in Major human populationsU01DK085545 · NIDDK · UNIVERSITY OF OXFORD · PI CHAN, JULIANA CN, EBRAHIM, SHAH BRIAN · 2009 to 2013
$2.8MDefining tumor cell and host adaptations in cancer progressionDP2CA248136 · NCI · YALE UNIVERSITY · PI MUZUMDAR, MANDAR DEEPAK · 2019 to 2019
$2.5MMedical Research Council MR/L020149/1NCATS NIH HHS KL2 TR001999NCATS NIH HHS UL1 TR001863NCI NIH HHS DP2 CA248136NCI NIH HHS K07 CA222159NCI NIH HHS K08 CA208016NCI NIH HHS L30 CA171131NCI NIH HHS P01 CA042063NCI NIH HHS P30 CA014051NCI NIH HHS P30 CA016359NCI NIH HHS P30 CA016672NCI NIH HHS U01 CA210171NIAID NIH HHS U19 AI089992NICHD NIH HHS F31 HD097958NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK110181NIDDK NIH HHS U01 DK085545NIDDK NIH HHS U01 DK105535NIGMS NIH HHS R01 GM130847NIGMS NIH HHS T32 GM007499NIH HHS S10 OD018521Wellcome Trust 090532Wellcome Trust 095101Wellcome Trust 098381Wellcome Trust 106130Wellcome Trust 200837Wellcome Trust 200837/Z/16/ZWellcome Trust 203141Wellcome Trust 212259
Abstract
Obesity is a major modifiable risk factor for pancreatic ductal adenocarcinoma (PDAC), yet how and when obesity contributes to PDAC progression is not well understood. Leveraging an autochthonous mouse model, we demonstrate a causal and reversible role for obesity in early PDAC progression, showing that obesity markedly enhances tumorigenesis, while genetic or dietary induction of weight loss intercepts cancer development. Molecular analyses of human and murine samples define microenvironmental consequences of obesity that foster tumorigenesis rather than new driver gene mutations, including significant pancreatic islet cell adaptation in obesity-associated tumors. Specifically, we identify aberrant beta cell expression of the peptide hormone cholecystokinin (Cck) in response to obesity and show that islet Cck promotes oncogenic Kras-driven pancreatic ductal tumorigenesis. Our studies argue that PDAC progression is driven by local obesity-associated changes in the tumor microenvironment and implicate endocrine-exocrine signaling beyond insulin in PDAC development.
Indexed as
AnimalsCarcinogenesisCarcinoma, Pancreatic DuctalCell LineCell Line, TumorCell Transformation, NeoplasticDisease Models, AnimalDisease ProgressionEndocrine CellsExocrine GlandsFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, Inbred C57BLbeta cellscholecystokiningenetically engineered mouse modelsleptinobesitypancreatic cancerpancreatic isletstumor microenvironment
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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 Socratic graph.