ArticleCell reports2019
Glutamine Anabolism Plays a Critical Role in Pancreatic Cancer by Coupling Carbon and Nitrogen Metabolism.
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Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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118citing papers in PubMed
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Who cites it
118 citing papers in PubMed, 188 citations in OpenAlex.
- The tumor microenvironment in pancreatic cancer: from composition to therapeutic targeting.Biochemical Society transactions · 2026Review
- MicroRNA-15a/16 regulate protein metabolism and are associated with clinical outcomes in pancreatic ductal adenocarcinoma.Physiological reports · 2026Article
- Mitochondrial inhibition enhances the sensitivity of pancreatic ductal adenocarcinoma cells to oncolytic adenovirus.Molecular therapy. Oncology · 2026Article
- Article
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Regulation of Autophagy and Metabolism in Hepatocellular Carcinoma: Involvement of Wnt-β-Catenin Pathway.Journal of cellular and molecular medicine · 2026Article
- Article
- Impaired nitrogenous waste clearance promotes hepatocellular carcinoma.Science advances · 2026Article
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Ammonia metabolic reprogramming in the tumor microenvironment: emergence of an immunosuppressive niche.Frontiers in cell and developmental biology · 2026Review
- FOXO1 links KRAS G12D and G12V alleles to glutamine and nitrogen metabolism in colorectal cancer.EMBO reports · 2026Article
- Ferroptosis in cancer: metabolism, mechanisms and therapeutic prospects.Molecular cancer · 2025Review
- Ammonia in cancer: dual roles and therapeutic strategies.Cancer cell international · 2025Review
- The integral membrane protein smim4 modulates redox balance via malate compartmentalization in pancreatic cancer.Nature communications · 2025Article
- Emerging Roles of De Novo Proline Biosynthesis in Human Diseases.FASEB bioAdvances · 2025Review
- Investigating stage-specific metabolic alterations in colorectal cancer through urine metabolomics.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- What's on the menu?: metabolic constraints in the pancreatic tumor microenvironment.The Journal of clinical investigation · 2025Review
- Drugging the 'undruggable' KRAS: breakthroughs, challenges, and opportunities in pancreatic cancer.Cancer biology & medicine · 2025Review
- HDAC6 and USP9X Control Glutamine Metabolism by Stabilizing GS to Promote Glioblastoma Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 9 institutions in 3 countries.
Alex J BottDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA; Genetics Graduate Program, Stony Brook University, Stony Brook, NY 07794, USA.
Jianliang ShenDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Claudia TonelliCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Le ZhanRutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
Nithya SivaramDepartment of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794, USA; Northport VA Medical Center, Northport, NY 11768, USA.
Ya-Ping JiangDepartment of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794, USA; Northport VA Medical Center, Northport, NY 11768, USA.
Xufen YuMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Vrushank BhattRutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
Eric ChilesRutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Hua ZhongDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Sara MaimouniDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Weiwei DaiDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Stephani VelasquezDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Ji-An PanDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Nathiya MuthalaguCRUK Beatson Institute, Glasgow G61 1BD, UK.
Jennifer MortonCRUK Beatson Institute, Glasgow G61 1BD, UK.
Tracy G AnthonyDepartment of Nutritional Sciences, Rutgers University, New Brunswick, NJ 08901, USA.
Hui FengDepartments of Pharmacology and Medicine, Section of Hematology and Medical Oncology, Cancer Research Center, Boston University School of Medicine, Boston, MA 02118, USA.
Wouter H LamersTytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Daniel J MurphyCRUK Beatson Institute, Glasgow G61 1BD, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow G61 1BD, UK.
Jessie Yanxiang GuoDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences and Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Howard C CrawfordDepartments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Lanjing ZhangDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Eileen WhiteRutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
Richard Z LinDepartment of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794, USA; Northport VA Medical Center, Northport, NY 11768, USA.
Xiaoyang SuRutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA; Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
David A TuvesonCold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Wei-Xing ZongDepartment of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA. Electronic address: zongwx@rutgers.edu.
Rutgers, The State University of New Jersey · USRutgers Cancer Institute of New JerseyCancer Research UK Scotland Institute · GBNorthport VA Medical Center · USCold Spring Harbor Laboratory · USIcahn School of Medicine at Mount Sinai · USAcademic Medical Center · NLBoston University · USUniversity of Michigan–Ann Arbor · US
Funding
Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI David A Tuveson · 1987 to 2026
$118.9MPancreatic Cancer Detection ConsortiumU01CA210240 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Michael A. Hollingsworth · 2017 to 2026
$12.9MUAB / UMN SPORE in Pancreatic CancerP50CA101955 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KLUG, CHRISTOPHER · 2010 to 2014
$11.1MHomeostatic Responses to Amino Acid InsufficiencyR01DK109714 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI ANTHONY, TRACY G., WEK, RONALD C · 2016 to 2024
$5.4MProtein and redox homeostasis in cancer development and therapyR01CA129536 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI ZONG, WEI-XING · 2008 to 2022
$4.8MGlutamine synthetase in cancer cell metabolism and oncogenesisR01CA224550 · NCI · RUTGERS, THE STATE UNIV OF N.J. · PI Wei-Xing Zong · 2018 to 2026
$4.7MCSHL-JAX Patient-Derived Models of Pancreatic Cancer as Systems for Investigating Tumor HeterogeneityU01CA224013 · NCI · COLD SPRING HARBOR LABORATORY · PI ROBSON, PAUL, TUVESON, DAVID A · 2018 to 2022
$4.2MNrf2 Regulation of Ductal Pancreatic Cancer Etiology and Treatment ResponseR01CA188134 · NCI · COLD SPRING HARBOR LABORATORY · PI TUVESON, DAVID A · 2017 to 2021
$3.0M(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
$2.0MThe Role of DLST in LeukemogenesisR01CA215059 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FENG, HUI · 2018 to 2022
$2.0MPI3 kinase PIK3CB (p110beta) in membrane trafficking and metabolismR01CA232246 · NCI · RUTGERS, THE STATE UNIV OF N.J. · PI ZONG, WEI-XING · 2018 to 2022
$1.8MCancer Research UK 29996NCI NIH HHS F99 CA212445NCI NIH HHS K22 CA190521NCI NIH HHS P20 CA192994NCI NIH HHS P20 CA192996NCI NIH HHS P30 CA045508NCI NIH HHS P50 CA101955NCI NIH HHS R01 CA129536NCI NIH HHS R01 CA188134NCI NIH HHS R01 CA190092NCI NIH HHS R01 CA215059NCI NIH HHS R01 CA224550NCI NIH HHS R01 CA232246NCI NIH HHS R21 CA205172NCI NIH HHS U01 CA210240NCI NIH HHS U01 CA224013NCI NIH HHS U10 CA180944NIDDK NIH HHS R01 DK109714
Abstract
Glutamine is thought to play an important role in cancer cells by being deaminated via glutaminolysis to α-ketoglutarate (aKG) to fuel the tricarboxylic acid (TCA) cycle. Supporting this notion, aKG supplementation can restore growth/survival of glutamine-deprived cells. However, pancreatic cancers are often poorly vascularized and limited in glutamine supply, in alignment with recent concerns on the significance of glutaminolysis in pancreatic cancer. Here, we show that aKG-mediated rescue of glutamine-deprived pancreatic ductal carcinoma (PDAC) cells requires glutamate ammonia ligase (GLUL), the enzyme responsible for de novo glutamine synthesis. GLUL-deficient PDAC cells are capable of the TCA cycle but defective in aKG-coupled glutamine biosynthesis and subsequent nitrogen anabolic processes. Importantly, GLUL expression is elevated in pancreatic cancer patient samples and in mouse PDAC models. GLUL ablation suppresses the development of Kras
Indexed as
AnimalsCarbonCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationFemaleGene DeletionGlutamate-Ammonia LigaseGlutamineHumansKetoglutaric AcidsMaleMice, Inbred C57BLNitrogenPancreatic NeoplasmsCarbonGlutamate-Ammonia LigaseGlutamineKetoglutaric AcidsNitrogenglutamate ammonia ligaseglutamineglutamine synthetasehexosamineK-Rasnitrogen metabolismnucleotidepancreatic cancerα-ketoglutarate
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