ArticleeLife2021
Hyaluronic acid fuels pancreatic cancer cell growth.
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Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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64citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
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Who cites it
64 citing papers in PubMed, 93 citations in OpenAlex.
- Understanding and targeting the tumour matrisome.Nature reviews. Clinical oncology · 2026Review
- A lysis-derived PMSF and orthovanadate oxidant defines a distinct cysteine-engagement profile.Cell chemical biology · 2026Article
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- Auranofin Suppresses Cancer Cell Invasion by Inhibiting Heparanase-1 Expression via the aPKC-NF-κB Pathway.International journal of molecular sciences · 2026Article
- Hyaluronan Underlies the Emergence of Form, Fate, and Function in Human Cardioids.bioRxiv : the preprint server for biology · 2026Article
- GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cryobioprinted human tumor models with shelf-stable programmability.Trends in biotechnology · 2026Article
- Bioengineered Pancreatic Cancer Immunosuppressive Microenvironment Models for Screening Immunotherapies.Advanced healthcare materials · 2026Article
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- The extracellular matrix drives guanylate production and protects pancreatic cancer cells from oxaliplatin-induced DNA damage.Science advances · 2025Article
- Impairment of Hyaluronan-Related Glycocalyx Inhibits Macropinocytosis in Cancer Cells via p21 Upregulation.Biomacromolecules · 2025Article
- Intracellular pH dynamics respond to extracellular matrix stiffening and mediate vasculogenic mimicry through β-catenin.Cell death & disease · 2025Article
- Mevalonate Biosynthesis is a Metabolic Vulnerability of Gemcitabine-resistant Pancreatic Cancer.bioRxiv : the preprint server for biology · 2025Article
- Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis.bioRxiv : the preprint server for biology · 2025Article
- Unraveling the glyco-immunity nexus in pancreatic cancer.Molecular cancer · 2025Review
- What's on the menu?: metabolic constraints in the pancreatic tumor microenvironment.The Journal of clinical investigation · 2025Review
- Intracellular pH dynamics respond to extracellular matrix stiffening and mediate vasculogenic mimicry through β-catenin.bioRxiv : the preprint server for biology · 2025Article
- Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells.The Journal of clinical investigation · 2025Article
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- Click Hydrogels to Assess Stiffness-Induced Activation of Pancreatic Cancer-Associated Fibroblasts and Its Impact on Cancer Cell Spreading.Chembiochem : a European journal of chemical biology · 2025Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Peter K Kim *Doctoral Program in Cancer Biology, University of Michigan, Ann Arbor, United States.ORCID 0000-0001-9382-7223
Christopher J Halbrook *Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Samuel A Kerk *Doctoral Program in Cancer Biology, University of Michigan, Ann Arbor, United States.
Megan RadykDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Stephanie WisnerDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Daniel M KremerDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Peter SajjakulnukitDoctoral Program in Cancer Biology, University of Michigan, Ann Arbor, United States.
Anthony AndrenDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Sean W HouDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Ayush TrivediDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Galloway ThurstonDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Abhinav AnandDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Liang YanDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States.
Lucia Salamanca-CardonaDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York City, United States.
Samuel D WellingDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Li ZhangDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.
Matthew R PrattDepartment of Chemistry, University of Southern California, Los Angeles, United States.ORCID 0000-0003-3205-5615
Kayvan R KeshariDepartment of Radiology, Memorial Sloan Kettering Cancer Center, New York City, United States.
Haoqiang YingDepartment of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, United States.
Costas A LyssiotisDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, United States.ORCID 0000-0001-9309-6141
University of Michigan · USMemorial Sloan Kettering Cancer Center · USThe University of Texas MD Anderson Cancer Center · USUniversity of Southern California · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MXenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2MUniversity of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OMARY, BISHR · 1986 to 2021
$22.5MStatistics and Bioinformatics Core - WangU24DK097153 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BURANT, CHARLES F · 2012 to 2017
$10.1MRESEARCH TRAINING IN EXPERIMENTAL IMMUNOPATHOLOGYT32AI007413 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Bethany B. Moore · 1993 to 2026
$9.8MTRAINING PROGRAM IN ORGANOGENESIST32HD007505 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PASCA DI MAGLIANO, MARINA, SPENCE, JASON · 1997 to 2021
$6.9MProteogenomics of Cancer Training ProgramT32CA140044 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAO, ARVIND, SARTOR, MAUREEN AGNES · 2010 to 2024
$3.9MDevelopment of large-field-of-view hyperpolarized MRIR01CA237466 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CUNNINGHAM, CHARLES H., HRICAK, HEDVIG · 2020 to 2024
$3.4MVisualizing oxidative stress using hyperpolarized magnetic resonanceR01CA252037 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI KESHARI, KAYVAN R · 2020 to 2024
$3.3MIntratumoral Metabolic Crosstalk Promotes Therapeutic Resistance in Pancreatic CancerR37CA237421 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Costas Andreas Lyssiotis · 2020 to 2026
$2.6MStromal metabolism promotes therapeutic resistance in pancreatic cancerR01CA248160 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LYSSIOTIS, COSTAS ANDREAS · 2020 to 2024
$2.0MTargeting metabolic stress to induce pancreatic tumor cell deathR01CA244931 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LYSSIOTIS, COSTAS ANDREAS · 2020 to 2024
$1.9MNCI NIH HHS Cancer Biology Training Grant,T32AI007413NCI NIH HHS Cancer Center Support Grant P30CA008748NCI NIH HHS Cancer Center Support Grant,P30CA008748NCI NIH HHS Cancer Center Support Grant P30 CA046592NCI NIH HHS Cancer Center Support Grant,P30 CA046592NCI NIH HHS F31 CA243344NCI NIH HHS F31CA24745701NCI NIH HHS F99 CA264414NCI NIH HHS F99/K00CA264414NCI NIH HHS K00 CA264414NCI NIH HHS K99 CA241357NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA046592NCI NIH HHS Pathway to Independence Award K99CA241357NCI NIH HHS Pathway to Independence Award,K99CA241357NCI NIH HHS Predoctoral Fellowship F31CA243344NCI NIH HHS Predoctoral Fellowship,F31CA243344NCI NIH HHS R00 CA241357NCI NIH HHS R01 CA237466NCI NIH HHS R01CA237466NCI NIH HHS R01 CA244931NCI NIH HHS R01CA244931NCI NIH HHS R01 CA248160NCI NIH HHS R01CA248160NCI NIH HHS R01 CA252037NCI NIH HHS R01CA252037NCI NIH HHS R21 CA212958NCI NIH HHS R21CA212958NCI NIH HHS R37 CA237421NCI NIH HHS R37CA237421NCI NIH HHS T32 CA140044NIAID NIH HHS T32 AI007413NICHD NIH HHS T32 HD007505NIDDK NIH HHS P30 DK034933NIDDK NIH HHS Postdoctoral Support P30DK034933NIDDK NIH HHS Postdoctoral Support,P30DK034933NIDDK NIH HHS U24 DK097153NIH HHS U24DK097153
Abstract
Rewired metabolism is a hallmark of pancreatic ductal adenocarcinomas (PDA). Previously, we demonstrated that PDA cells enhance glycosylation precursor biogenesis through the hexosamine biosynthetic pathway (HBP) via activation of the rate limiting enzyme, glutamine-fructose 6-phosphate amidotransferase 1 (GFAT1). Here, we genetically ablated GFAT1 in human PDA cell lines, which completely blocked proliferation in vitro and led to cell death. In contrast, GFAT1 knockout did not preclude the growth of human tumor xenografts in mice, suggesting that cancer cells can maintain fidelity of glycosylation precursor pools by scavenging nutrients from the tumor microenvironment. We found that hyaluronic acid (HA), an abundant carbohydrate polymer in pancreatic tumors composed of repeating
Indexed as
AdenocarcinomaAnimalsCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationFemaleGene Knockout TechniquesGlutamine-Fructose-6-Phosphate Transaminase (Isomerizing)HexosaminesHumansHyaluronic AcidMaleMiceMice, Inbred NODMice, SCIDTransplantation, HeterologousGlutamine-Fructose-6-Phosphate Transaminase (Isomerizing)HexosaminesHyaluronic Acidcancer biologyextracellular matrixhexosamine biosynthetic pathwayhumanhyaluronic acidmousepancreatic cancertumor metabolismtumor microenvironment
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