ArticleCell2016
NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer.
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Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 238 papers, 2 of them syntheses that pooled it.
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238citing papers in PubMed, 2 pooled it
22.6field-weighted citation impact, top 1% of its field
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Who cites it
238 citing papers in PubMed, 2 syntheses or guidelines pooled it, 379 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review.Cell communication and signaling : CCS · 2019Pooled it
- Diet-Induced Phospholipid Remodeling Dictates Ferroptosis Sensitivity and Tumorigenesis in the Pancreas.Cancer discovery · 2026Article
- Gambogenic acid globally regulates translational processes in Nrf2-mutant esophageal squamous cell carcinoma by promoting Nrf2/MafG protein multimerization.Acta pharmacologica Sinica · 2026Article
- Hypoxia-induced metastatic heterogeneity in pancreatic cancer.Nature communications · 2026Article
- Refining antibiotic cocktail regimens for pseudo-germ-free mice and their impact on gut microbiome and pancreatic tumor proteomics.Journal of advanced research · 2026Article
- NADPH-producing enzymes restrict the formation of pancreatic precancerous lesions.Nature metabolism · 2026Article
- Evaluating the implications of K-Ras, KEAP1/NRF2-mediated signaling pathways and metabolic alterations in urethane-induced lung cancer.Journal of molecular histology · 2026Article
- Study on the Mechanism of FOXA2 Activation on Glutathione Metabolic Reprogramming Mediated by ETV4 Transcription to Facilitate Colorectal Cancer Malignant Progression.Biochemical genetics · 2025Article
- Hypoxia-induced metastatic heterogeneity in pancreatic cancer.Research square · 2025Article
- Nrf2 Drives Epigenetic Reprogramming and Acts as the Master Regulator of KLF4 Expression and Activity in Arsenic-Induced Transformation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Effects of antioxidants on cancer progression.EMBO molecular medicine · 2025Review
- Correlations of phosphorylated Nrf2 with responses to neoadjuvant chemotherapy in patients with triple-negative breast cancer.BMC women's health · 2025Observational
- Review
- Self-amplifying NRF2-EZH2 epigenetic loop converts KRAS-initiated progenitors to invasive pancreatic cancer.Nature cancer · 2025Article
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Dual Role of NRF2 in Pancreatic Precursor Lesions.Cancer research communications · 2025Article
- Dysregulated ribosome quality control in human diseases.The FEBS journal · 2025Review
- OASL promotes immune evasion in pancreatic ductal adenocarcinoma by enhancing autolysosome-mediated degradation of MHC-I.Theranostics · 2025Article
- Developing a prognostic stratification model based on glutathione metabolism in thyroid cancer and validating RRM2's tumor-promoting role.Frontiers in oncology · 2025Article
178 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 9 institutions in 2 countries.
Iok In Christine ChioCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
Seyed Mehdi JafarnejadDepartment of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
Mariano Ponz-SarviseCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
Youngkyu ParkCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
Keith RiveraCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Wilhelm PalmCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
John WilsonCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Vineet SangarInstitute of Systems Biology, 401 Terry Avenue N, Seattle, WA 98109, USA.
Yuan HaoCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Daniel ÖhlundCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
Kevin WrightCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
Dea FilippiniCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
Eun Jung LeeCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
Brandon Da SilvaCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
Christina SchoepferCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
John Erby WilkinsonDepartments of Molecular & Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Jonathan M BuscagliaDivision of Gastroenterology, Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY 11794, USA.
Gina M DeNicolaMeyer Cancer Center, Weill Cornell Medical College, New York, NY 10021, USA.
Herve TiriacCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA.
Molly HammellCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Howard C CrawfordDepartments of Molecular & Integrative Physiology and Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Edward E SchmidtDepartment of Microbiology and Immunology, Montana State University, Bozeman, MT 59718, USA.
Craig B ThompsonCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Darryl J PappinCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Nahum SonenbergDepartment of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada.
David A TuvesonCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY 11724, USA. Electronic address: dtuveson@cshl.edu.
Cold Spring Harbor Laboratory · USLustgarten Foundation · USMcGill University · CAMemorial Sloan Kettering Cancer Center · USUniversity of Michigan–Ann Arbor · USCornell University · USInstitute for Systems Biology · USMontana State University · USStony Brook University · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MSingle-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9MUAB / UMN SPORE in Pancreatic CancerP50CA101955 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BUCHSBAUM, DONALD J · 2010 to 2014
$11.1MCOMPUTATIONAL AND FUNCTIONAL APPROACHES TO VALIDATING CANCER GENOME TARGETSU01CA168409 · NCI · COLD SPRING HARBOR LABORATORY · PI POWERS, SCOTT · 2012 to 2016
$7.3M(PQA-4) Organoid Omics To Detect And Defeat Ductal Pancreatic CancerR01CA190092 · NCI · COLD SPRING HARBOR LABORATORY · PI TUVESON, DAVID A · 2014 to 2017
$2.2MIntegrated Translational Cancer Science CenterU10CA180944 · NCI · COLD SPRING HARBOR LABORATORY · PI BAKER, LAURENCE HOWARD, LIU, EDISON TAK-BUN · 2014 to 2018
$2.0MADAM17 in pancreatic cancer and pancreatitisR01CA159222 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CRAWFORD, HOWARD C. · 2011 to 2015
$1.9MThe Paradoxical Role of mTORC1 in the Growth of Nutrient-deprived Pancreatic Cancer Cells Harboring Ras MutationsR01CA201318 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI THOMPSON, CRAIG B · 2016 to 2020
$1.7MImpact of hepatocyte lineage life history dynamics on liver homeostasis in the agR01AG040020 · NIA · MONTANA STATE UNIVERSITY - BOZEMAN · PI GEDEON, TOMAS, SCHMIDT, EDWARD E · 2011 to 2015
$1.5MRedox regulation in the hepatostatR21AG055022 · NIA · MONTANA STATE UNIVERSITY - BOZEMAN · PI ARNER, ELIAS S.J., NAGY, PETER · 2016 to 2017
$382kInitiation, persistence, and progression of hepatocellular carcinomaR21CA152559 · NCI · MONTANA STATE UNIVERSITY - BOZEMAN · PI SCHMIDT, EDWARD E · 2010 to 2011
$310kCIHRNCI NIH HHS P30 CA008748NCI NIH HHS P30 CA045508NCI NIH HHS P50 CA101955NCI NIH HHS R01 CA159222NCI NIH HHS R01 CA190092NCI NIH HHS R01 CA201318NCI NIH HHS R21 CA152559NCI NIH HHS U01 CA168409NCI NIH HHS U10 CA180944NIA NIH HHS R01 AG040020NIA NIH HHS R21 AG055022
Abstract
Pancreatic cancer is a deadly malignancy that lacks effective therapeutics. We previously reported that oncogenic Kras induced the redox master regulator Nfe2l2/Nrf2 to stimulate pancreatic and lung cancer initiation. Here, we show that NRF2 is necessary to maintain pancreatic cancer proliferation by regulating mRNA translation. Specifically, loss of NRF2 led to defects in autocrine epidermal growth factor receptor (EGFR) signaling and oxidation of specific translational regulatory proteins, resulting in impaired cap-dependent and cap-independent mRNA translation in pancreatic cancer cells. Combined targeting of the EGFR effector AKT and the glutathione antioxidant pathway mimicked Nrf2 ablation to potently inhibit pancreatic cancer ex vivo and in vivo, representing a promising synthetic lethal strategy for treating the disease.
Indexed as
Protein BiosynthesisAnimalsAutocrine CommunicationCysteineGlutathioneHumansMiceNF-E2-Related Factor 2OrganoidsPancreatic NeoplasmsProto-Oncogene Proteins p21(ras)Signal TransductionCysteineGlutathioneKRAS protein, humanNFE2L2 protein, humanNF-E2-Related Factor 2Proto-Oncogene Proteins p21(ras)
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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.