ArticleCell metabolism2023
Neutrophils resist ferroptosis and promote breast cancer metastasis through aconitate decarboxylase 1.
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Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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149citing papers in PubMed
30.4field-weighted citation impact, top 1% of its field
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Who cites it
149 citing papers in PubMed, 185 citations in OpenAlex.
- Robust structural, kinetic and biophysical characterization of wild-type human ACOD1, selected mutants and their interaction with citraconate.Journal of structural biology: X · 2026Article
- Neutrophil-driven immunosuppression in cancer.Cell insight · 2026Review
- Itaconate metabolism in regulated cell death.Molecular and cellular biochemistry · 2026Review
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- PACT Inhibits Malignant Biological Behavior of Ovarian Cancer Cells by Regulating TERT Expression.Molecular carcinogenesis · 2026Article
- Ferroptosis in T cells: mechanisms, biology and translational opportunities.Nature reviews. Immunology · 2026Review
- Neutrophil-based immunotherapy: A metabolic lens on mechanisms and therapeutic implications.Clinical and translational medicine · 2026Review
- Breaking the immune "cold niche" in bone metastasis: core mechanisms of the multidimensional interwoven regulatory network and precision breakthrough strategies.Molecular cancer · 2026Review
- Obesity suppresses neutrophil-dependent itaconate signaling promoting ferroptosis in acute pancreatitis.Redox biology · 2026Article
- Tumor cell ferroptosis in antitumor immunity and immunotherapy efficacy.Journal for immunotherapy of cancer · 2026Review
- Programmed cell death and metastatic evolution in breast cancer: the role of anoikis, necroptosis, and ferroptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Endoplasmic reticulum stress in brain metastatic cascade.NPJ precision oncology · 2026Review
- Review
- Ferroptosis in breast cancer: From adipocyte-immune-iron regulation to therapeutic application.Clinical and translational medicine · 2026Review
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- Metabolic adaptations of immunosuppressive cells in cancer: mechanisms and therapeutic targets.Experimental & molecular medicine · 2026Review
- Neutrophil Irgm1 ameliorates sepsis-induced myocardial dysfunction by promoting Alox15 degradation.Redox biology · 2026Article
- Peroxiredoxin 4 suppresses ferroptosis in esophageal squamous cell carcinoma by activating the phosphoinositide 3-kinase signaling pathway.Biomedical reports · 2026Article
- ACOD1-itaconate in macrophage attenuates oxidative stress and inflammation in benign airway stenosis by upregulating and transferring FTH1.Redox biology · 2026Article
89 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 5 institutions in 1 country.
Yun ZhaoDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Zhongshun LiuDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Guoqiang LiuDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
Yuting ZhangDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
Sheng LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Dailin GanDepartment of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA.
Wennan ChangDepartment of Medical and Molecular Genetics and Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Electrical and Computer Engineering, Purdue University, Indianapolis, IN 46202, USA.
Xiaoxia PengDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Eun Suh SungDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Keegan GilbertDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Yini ZhuDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
Xuechun WangDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Ziyu ZengDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Hope BaldwinDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Guanzhu RenDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Jessica WeaverDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Anna HuronDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Toni MayberryHarper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Qingfei WangDivision of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Yujue WangRutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
Maria Elena Diaz-RubioRutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, 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.
M Sharon StackHarper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Siyuan ZhangDepartment of Pathology, Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Xuemin LuDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA.
Ryan D SheldonMass Spectrometry Core, Van Andel Institute, Grand Rapids, MI, USA.
Jun LiDepartment of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA.
Chi ZhangDepartment of Medical and Molecular Genetics and Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Electrical and Computer Engineering, Purdue University, Indianapolis, IN 46202, USA.
Jun WanDepartment of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN 46202, USA; School of Informatics and Computing, Indiana University - Purdue University at Indianapolis, Indianapolis, IN 46202, USA.
Xin LuDepartment of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA; Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA; Tumor Microenvironment and Metastasis Program, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA. Electronic address: xlu@nd.edu.
University of Notre Dame · USRutgers, The State University of New Jersey · USIndiana University School of MedicineThe University of Texas Southwestern Medical Center · USUniversity of Indianapolis · US
Funding
Tumor Microenvironment and Metastasis ProgramP30CA082709 · NCI · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI Reuben Kapur · 1999 to 2026
$59.3MReceptor Cross-Talk in Early Metastatic DisseminationR01CA109545 · NCI · UNIVERSITY OF NOTRE DAME · PI STACK, MARY SHARON · 2006 to 2022
$4.3MConverting Cold to Hot Tumor Microenvironment in Prostate Cancer by Targeting Chromatin EffectorR01CA248033 · NCI · UNIVERSITY OF NOTRE DAME · PI LU, XIN · 2020 to 2024
$1.8MImmunosuppression and Metabolic Rewiring in Tumor-infiltrating NeutrophilsR01CA280097 · NCI · UNIVERSITY OF NOTRE DAME · PI Xin Lu · 2023 to 2026
$1.4MNCI NIH HHS P30 CA082709NCI NIH HHS R01 CA109545NCI NIH HHS R01 CA248033NCI NIH HHS R01 CA280097
Abstract
Metastasis causes breast cancer-related mortality. Tumor-infiltrating neutrophils (TINs) inflict immunosuppression and promote metastasis. Therapeutic debilitation of TINs may enhance immunotherapy, yet it remains a challenge to identify therapeutic targets highly expressed and functionally essential in TINs but under-expressed in extra-tumoral neutrophils. Here, using single-cell RNA sequencing to compare TINs and circulating neutrophils in murine mammary tumor models, we identified aconitate decarboxylase 1 (Acod1) as the most upregulated metabolic enzyme in mouse TINs and validated high Acod1 expression in human TINs. Activated through the GM-CSF-JAK/STAT5-C/EBPβ pathway, Acod1 produces itaconate, which mediates Nrf2-dependent defense against ferroptosis and upholds the persistence of TINs. Acod1 ablation abates TIN infiltration, constrains metastasis (but not primary tumors), bolsters antitumor T cell immunity, and boosts the efficacy of immune checkpoint blockade. Our findings reveal how TINs escape from ferroptosis through the Acod1-dependent immunometabolism switch and establish Acod1 as a target to offset immunosuppression and improve immunotherapy against metastasis.
Indexed as
Breast NeoplasmsCarboxy-LyasesFerroptosisAnimalsCutaneous Malignant MelanomaFemaleHumansHydro-LyasesMiceNeutrophilsAcod1 protein, mouseaconitate decarboxylaseCarboxy-LyasesHydro-LyasesAcod1breast cancerferroptosisimmune checkpoint blockadeimmune metabolismitaconateMDSCmetastasisneutrophilsingle-cell RNA sequencing
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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.