ArticleRedox biology2023
A pan-cancer analysis shows immunoevasive characteristics in NRF2 hyperactive squamous malignancies.
Article in Redox biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 43 citations in OpenAlex.
- Clinicopathological characteristics of patients with inoperable non-small cell lung cancer harboring circulating NRF2 pathway mutations.The Journal of pathology · 2026Article
- Exploring and experimental validation of SLC7A11 and ferroptosis related prognostic genes in non-small cell lung cancer using bulk RNA sequencing and single-cell RNA sequencing.Biology direct · 2026Article
- Multi-omics profiling revealsTranslational lung cancer research · 2026Article
- Systematic Pan-Cancer Analysis of the Oncogenic and Immunological Function of Stanniocalcin-1 (STC1).Current medicinal chemistry · 2026Article
- Hot-yet-suppressed under PD-1 blockade: an RMP-NRF2-PD-L1 axis associated with a reduced proportional response in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- Single-cell transcriptomic analysis of cutaneous squamous cell carcinoma identifies an NR1H3-associated angiogenic macrophage state.Frontiers in immunology · 2026Article
- NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting.Oncogene · 2025Review
- Nicotinamide phosphoribosyltransferase in NADCell death discovery · 2025Review
- Silibinin Anticancer Effects Through the Modulation of the Tumor Immune Microenvironment in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Molecular signatures of disulfidptosis: interplay with programmed cell death pathways and therapeutic implications in oncology.Cellular & molecular biology letters · 2025Review
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Oxygen needs sulfur, sulfur needs oxygen: a relationship of interdependence.The EMBO journal · 2025Review
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
- YAP1 activates SLC2A1 transcription and augments the malignant behavior of colorectal cancer cells by activating the Wnt/β-catenin signaling pathway.Cell division · 2025Article
- Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.Redox biology · 2025Review
- Targeting novel regulated cell death: disulfidptosis in cancer immunotherapy with immune checkpoint inhibitors.Biomarker research · 2025Review
- Article
- Pan-Cancer Analysis of GPR141: Unveiling its prognostic significance, immune microenvironment interactions, and therapeutic potential.Journal of Cancer · 2025Article
- Splicing junction-based classifier for the detection of abnormal constitutive activation of the KEAP1-NRF2 system.NPJ systems biology and applications · 2024Article
- Mitochondrial disruption resulting from Cepharanthine-mediated TOM inhibition triggers ferroptosis in colorectal cancer cells.Journal of cancer research and clinical oncology · 2024Article
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NRF2 pathway is frequently activated in various cancer types, yet a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a NRF2 activity metric and utilized it to conduct a pan-cancer analysis of oncogenic NRF2 signaling. We identified an immunoevasive phenotype where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression and T cell and macrophage infiltration in squamous malignancies of the lung, head and neck area, cervix and esophagus. Squamous NRF2 overactive tumors comprise a molecular phenotype with SOX2/TP63 amplification, TP53 mutation and CDKN2A loss. These immune cold NRF2 hyperactive diseases are associated with upregulation of immunomodulatory NAMPT, WNT5A, SPP1, SLC7A11, SLC2A1 and PD-L1. Based on our functional genomics analyses, these genes represent candidate NRF2 targets, suggesting direct modulation of the tumor immune milieu. Single-cell mRNA data shows that cancer cells of this subtype exhibit decreased expression of IFNγ responsive ligands, and increased expression of immunosuppressive ligands NAMPT, SPP1 and WNT5A that mediate signaling in intercellular crosstalk. In addition, we discovered that the negative relationship of NRF2 and immune cells are explained by stromal populations of lung squamous cell carcinoma, and this effect spans multiple squamous malignancies based on our molecular subtyping and deconvolution data.
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