ArticleCell death & disease2023
Interferon-gamma is quintessential for NOS2 and COX2 expression in ER
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Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Nitric oxide-driven Warburg reprogramming at the NOS2-COX2 axis: An integrative engine of cancer hallmarks.Redox biology · 2026Review
- NOS2 and COX2 impact the spatial landscape of CD8Redox biology · 2026Review
- S-nitrosylated COX-2 is a microenvironment-regulated breast cancer cell biomarker of mesenchymal phenotypes.Experimental cell research · 2026Article
- Elevated tumor NOS2/COX2 promotes immunosuppressive phenotypes associated with poor survival in ER- breast cancer.JCI insight · 2025Article
- The Role of Nitric Oxide in Cancer Treatment: Ally or Foe?Molecules (Basel, Switzerland) · 2025Review
- Neuropilin-2-expressing breast cancer cells mitigate radiation-induced oxidative stress through nitric oxide signaling.The Journal of clinical investigation · 2024Article
- Tumor NOS2 and COX2 Spatial Juxtaposition with CD8+ T Cells Promote Metastatic and Cancer Stem Cell Niches that Lead to Poor Outcome in ER- Breast Cancer.Cancer research communications · 2024Article
- NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer.International journal of molecular sciences · 2024Review
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- Spatial analysis of NOS2 and COX2 interaction with T-effector cells reveals immunosuppressive landscapes associated with poor outcome in ER- breast cancer patients.bioRxiv : the preprint server for biology · 2023Article
- NOS2 and COX2 Provide Key Spatial Targets that Determine Outcome in ER- Breast Cancer.bioRxiv : the preprint server for biology · 2023Article
- Nitric oxide inhibits FTO demethylase activity to regulate NRedox biology · 2023Article
Corrections and comments
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Authors and funding
25 authors at 11 institutions in 3 countries.
Robert Y S Cheng *Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.ORCID 0000-0003-0287-6439
Lisa A Ridnour *Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.ORCID 0000-0001-9446-8349
Adelaide L WinkOptical Microscopy and Analysis Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. for the National Cancer Institute, Frederick, MD, USA.
Ana L GonzalezCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Elise L FeminoCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Helene RittscherCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Veena SomasundaramCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
William F HeinzOptical Microscopy and Analysis Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. for the National Cancer Institute, Frederick, MD, USA.ORCID 0000-0002-6194-0536
Leandro CoutinhoCenter for Translational Research in Oncology, ICESP/HC, Faculdade de Medicina da Universidade de São Paulo; and Comprehensive Center for Precision Oncology, Universidade de São Paulo, São Paulo, SP, Brazil.
M Cristina RangelCenter for Translational Research in Oncology, ICESP/HC, Faculdade de Medicina da Universidade de São Paulo; and Comprehensive Center for Precision Oncology, Universidade de São Paulo, São Paulo, SP, Brazil.ORCID 0000-0002-8002-9617
Elijah F EdmondsonMolecular Histopathology Laboratories, Leidos Biomedical Research Inc. for NCI, Frederick, MD, USA.
Donna ButcherMolecular Histopathology Laboratories, Leidos Biomedical Research Inc. for NCI, Frederick, MD, USA.
Robert J KindersOffice of the Director, Division of Cancer Treatment and Diagnosis, NCI, Frederick, MD, USA.
Xiaoxian LiDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
Stephen T C WongSystems Medicine and Bioengineering Department, Houston Methodist Neal Cancer Center, Houston Methodist Hospital and Weill Cornell Medicine, Houston, TX, USA.
Daniel W McVicarCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Stephen K AndersonCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Milind PoreImaging Mass Cytometry Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Stephen M HewittLaboratory of Pathology CCR, NCI, NIH, Bethesda, MD, USA.ORCID 0000-0001-8283-1788
Timothy R BilliarDepartment of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.ORCID 0000-0002-2949-0811
Sharon A GlynnDiscipline of Pathology, Lambe Institute for Translational Research, School of Medicine, University of Galway, Galway, Ireland.
Jenny C ChangMary and Ron Neal Cancer Center, Houston Methodist Hospital and Weill Cornell Medicine, Houston, TX, USA.
Stephen J LockettOptical Microscopy and Analysis Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. for the National Cancer Institute, Frederick, MD, USA.ORCID 0000-0002-2010-9914
Stefan AmbsLaboratory of Human Carcinogenesis, CCR, NCI, NIH, Bethesda, MD, USA.ORCID 0000-0001-7651-9309
David A WinkCancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA. wink@mail.nih.gov.ORCID 0000-0002-5652-7480
National Institutes of Health · USLeidos (United States) · USUniversidade de São Paulo · BRCenter for Cancer Research · USCornell University · USEmory University · USFrederick National Laboratory for Cancer Research · USHouston Methodist · USOffice of the Director · USOllscoil na Gaillimhe – University of Galway · IEUniversity of Pittsburgh Medical Center · US
Funding
WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6MSignal Transduction of Paired Inhibitory Receptors of NK Cells and MacrophagesZIABC010300 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MCVICAR, DANIEL W. · 2009 to 2025
$24.6MMolecular Studies of Cellular CytotoxicityZIABC010013 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ANDERSON, STEPHEN K · 2009 to 2025
$17.2MExperimental Pathology Laboratory (EPL)ZICBC011638 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HEWITT, STEPHEN · 2015 to 2025
$16.6MNovel Markers for Disease Outcome in Breast CancerZIABC010887 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI AMBS, STEFAN · 2009 to 2025
$11.5MTransport Oncophysics CoreU54CA210181 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI CHANG, JENNY C-N, SHEN, HAIFA · 2016 to 2020
$9.3MNitric Oxide as a Modifier of Oxidative StressZIASC007281 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI WINK, DAVID · 2009 to 2025
$8.1MProperties of redox modified NSAIDs in cancer prevention and treatmentZIABC010899 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WINK, DAVID · 2009 to 2025
$6.7MSpatiotemporal modeling of cancer-niche interactions in breast cancer bone metastasisU01CA253553 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI WONG, STEPHEN TC, ZHANG, XIANG · 2020 to 2024
$3.0MSystematic identification of astrocyte-tumor crosstalk regulating brain metastatic tumorsR01CA238727 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI WONG, STEPHEN TC, ZHAO, HONG · 2020 to 2024
$2.6MCCR NIH HHS HHSN261200800001CNCI NIH HHS 75N91019D00024NCI NIH HHS HHSN261200800001ENCI NIH HHS R01 CA238727NCI NIH HHS U01 CA253553NCI NIH HHS U54 CA210181NIH HHS 75N91019D00024NIH HHS HHSN261200800001E
Abstract
A strong correlation between NOS2 and COX2 tumor expression and poor clinical outcomes in ER breast cancer has been established. However, the mechanisms of tumor induction of these enzymes are unclear. Analysis of The Cancer Genome Atlas (TCGA) revealed correlations between NOS2 and COX2 expression and Th1 cytokines. Herein, single-cell RNAseq analysis of TNBC cells shows potent NOS2 and COX2 induction by IFNγ combined with IL1β or TNFα. Given that IFNγ is secreted by cytolytic lymphocytes, which improve clinical outcomes, this role of IFNγ presents a dichotomy. To explore this conundrum, tumor NOS2, COX2, and CD8
Indexed as
Interferon-gammaTriple Negative Breast NeoplasmsTumor MicroenvironmentCD8-Positive T-LymphocytesCell Line, TumorCyclooxygenase 2FemaleHumansNitric Oxide Synthase Type IITumor Necrosis Factor-alphaCyclooxygenase 2Interferon-gammaNitric Oxide Synthase Type IINOS2 protein, humanTumor Necrosis Factor-alpha
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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.