ArticleCancer cell2017
MUC1 and HIF-1alpha Signaling Crosstalk Induces Anabolic Glucose Metabolism to Impart Gemcitabine Resistance to Pancreatic Cancer.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Cancer cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 309 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
309citing papers in PubMed, 2 pooled it
15.7field-weighted citation impact, top 1% of its field
What it found
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Who cites it
309 citing papers in PubMed, 2 syntheses or guidelines pooled it, 539 citations in OpenAlex.
- Current hotspots and trends in cancer metabolic reprogramming: a scientometric analysis.Frontiers in immunology · 2024Pooled it
- Association of mucin family members with prognostic significance in pancreatic cancer patients: A meta-analysis.PloS one · 2022Pooled it
- Elesclomol-mediated cuproptosis overcomes cisplatin resistance by restricting epigenetically activated mitochondrial respiration: Novel therapeutic insights into cisplatin-elesclomol combination therapy.Acta pharmaceutica Sinica. B · 2026Article
- Systemic immunosuppression limits NK cell therapy efficacy in pancreatic cancer.Molecular cancer · 2026Article
- MicroRNA-15a/16 regulate protein metabolism and are associated with clinical outcomes in pancreatic ductal adenocarcinoma.Physiological reports · 2026Article
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Mitochondrial-Localized Keratin 17 Promotes Chemoresistance in Basal-like Pancreatic Cancer.Cancer research · 2026Article
- Biomimetic nanomodulator reprograms glycolysis-driven immunosuppressive microenvironment to potentiate photothermal immunotherapy in cold tumors.Materials today. Bio · 2026Article
- Oligometastatic Prostate Cancer: Clues from an N-of-1.Journal of clinical medicine · 2026Article
- Normoxic HIFα-mediated metabolic rewiring in cancer as a novel therapeutic target of tumor heterogeneity.Cancer & metabolism · 2026Article
- Activatable nanoflytrap achieves synergistic "Capture-Block-Regulate" therapy of pancreatic ductal adenocarcinoma.Journal of nanobiotechnology · 2026Article
- Metabolic drivers of genome instability in cancer: mechanisms and therapeutic opportunities.Experimental hematology & oncology · 2026Review
- Evolution of the MUC1 gene in eutherian mammals as an adaptation responsible for the increasing incidence of cancer in humans.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- Review
- Responsive nanomedicine strategies achieve pancreatic cancer precise theranostics.Bioactive materials · 2026Review
- Multi-omics analysis identifies GAA as an independent poor prognostic biomarker and candidate therapeutic target in angioimmunoblastic T-cell lymphoma.Frontiers in immunology · 2026Article
- Mechanistic role of glycolytic pathways in the tumor microenvironment in driving chemoresistance.Frontiers in cell and developmental biology · 2026Review
249 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
37 authors at 10 institutions in 2 countries.
Surendra K ShuklaEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Vinee PurohitEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Kamiya MehlaEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Venugopal GundaEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Nina V ChaikaEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Enza VernucciEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Ryan J KingEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Jaime AbregoEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Gennifer D GoodeEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Aneesha DasguptaEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Alysha L IlliesEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Teklab GebregiworgisDepartment of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Bingbing DaiDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jithesh J AugustineDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Divya MurthyEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Kuldeep S AttriEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Oksana MashadovaDepartment of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Paul M GrandgenettEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Robert PowersDepartment of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
Quan P LyDepartment of Surgery, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Audrey J LazenbyDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Jean L GremDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Fang YuDepartment of Biostatistics, University of Nebraska Medical Center, Omaha, NE 68198, USA.
José M MatésDepartment of Molecular Biology and Biochemistry, University of Málaga and IBIMA, 29071 Málaga, Spain.
John M AsaraDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Jung-Whan KimDepartment of Biological Sciences, The University of Texas at Dallas, 800 West Campbell Road, Richardson, TX 75080, USA.
Jordan H HankinsDepartment of Radiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Colin WeekesDivision of Medical Oncology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Michael A HollingsworthEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Natalie J SerkovaDepartment of Anesthesiology, University of Colorado Denver, Aurora, CO 80045, USA.
Aaron R SassonDepartment of Surgery, Health Sciences Center T18-065, Stony Brook Medicine, Stony Brook, NY 11794, USA.
Jason B FlemingDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jennifer M OlivetoDepartment of Radiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Costas A LyssiotisDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48103, USA.
Lewis C CantleyDepartment of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
Lyudmyla BerimDepartment of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Pankaj K SinghEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: pankaj.singh@unmc.edu.
University of Nebraska Medical Center · USThe University of Texas MD Anderson Cancer Center · USCornell University · USUniversity of Colorado Denver · USUniversity of Nebraska–Lincoln · USHarvard University · USInstituto de Investigación Biomédica de Málaga · ESStony Brook Medicine · USThe University of Texas at Dallas · USUniversity of Michigan–Ann Arbor · US
Funding
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0MUNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Apar Kishor Ganti · 1985 to 2026
$55.0MThe RAS and P13K Pathways in Pancreatic AdenocarcinomaP01CA117969 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DEPINHO, RONALD ANTHONY · 2006 to 2025
$41.7MTissue CoreP50CA127297 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI HOLLINGSWORTH, MICHAEL A. · 2008 to 2018
$17.1MTargeting Tumor-Stromal Metabolic Cross-Talk in Pancreatic CancerR01CA163649 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Pankaj Kumar Singh · 2012 to 2026
$5.4MResearch Pilot Project ProgramP30GM106397 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI JOHNSON, KEITH R · 2013 to 2017
$4.9MRole of N-Cadherin in Pancreatic Tumor MicroenvironmentU54CA163120 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2011 to 2015
$4.2MMetabolic Regulation of Tumor Progression, Metastasis and Chemoresistance by SIRT5/ELK3 signaling in Pancreatic CancerR01CA216853 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SINGH, PANKAJ KUMAR · 2017 to 2021
$2.6MTargeting the Metabolic Basis of Cachexia in Pancreatic CancerR01CA210439 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI SINGH, PANKAJ KUMAR · 2017 to 2021
$2.6MCritical Resources Provided by UNMC Rapid Autopsy Program (RAP) Biorepository Stimulate Cancer ResearchR50CA211462 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Paul M Grandgenett · 2016 to 2026
$1.4MNCI NIH HHS P01 CA117969NCI NIH HHS P30 CA036727NCI NIH HHS P30 CA046934NCI NIH HHS P50 CA127297NCI NIH HHS R01 CA163649NCI NIH HHS R01 CA210439NCI NIH HHS R01 CA216853NCI NIH HHS R50 CA211462NCI NIH HHS U54 CA163120NIGMS NIH HHS P30 GM106397
Abstract
Poor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition. We also demonstrate that MUC1-regulated stabilization of hypoxia inducible factor-1α (HIF-1α) mediates such metabolic reprogramming. Targeting HIF-1α or de novo pyrimidine biosynthesis, in combination with gemcitabine, strongly diminishes tumor burden. Finally, reduced expression of TKT and CTPS, which regulate flux into pyrimidine biosynthesis, correlates with better prognosis in pancreatic cancer patients on fluoropyrimidine analogs.
Indexed as
Drug Resistance, NeoplasmCarbonDeoxycytidineDigoxinGemcitabineGlucoseHumansHypoxia-Inducible Factor 1, alpha SubunitMucin-1Pancreatic NeoplasmsPentose Phosphate PathwayPrognosisPyrimidinesSignal TransductionCarbonDeoxycytidineDigoxinGemcitabineGlucoseHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitMUC1 protein, humanMucin-1pyrimidinePyrimidinescancer metabolismchemotherapy resistancegemcitabineHIF-1αMUC1mucinnon-oxidative pentose phosphate pathwaynucleotide synthesispancreatic cancerpyrimidine biosynthesis
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