ArticleCancer science2020
Impacts of NRF2 activation in non-small-cell lung cancer cell lines on extracellular metabolites.
Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Multi-omics analysis identifies a major histocompatibility complex class II-associated antigen-presenting cancer-associated fibroblast-like state linked to the nuclear factor erythroid 2-related factor 2-karyopherin subunit beta 1 axis in nonsmall cell lung cancer.Journal of cell communication and signaling · 2026Article
- NRF2 immunobiology in cancer: implications for immunotherapy and therapeutic targeting.Oncogene · 2025Review
- Brassinin from Brassica campestris L. inhibits colorectal cancer by inducing p62/NRF2/GPX4-regulated ferroptosis.Animal models and experimental medicine · 2025Article
- Supersulfide metabolome of exhaled breath condensate applied as diagnostic biomarkers for esophageal cancer.Cancer science · 2025Article
- Splicing junction-based classifier for the detection of abnormal constitutive activation of the KEAP1-NRF2 system.NPJ systems biology and applications · 2024Article
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- PPIA dictates NRF2 stability to promote lung cancer progression.Nature communications · 2024Article
- Biomarkers of NRF2 signalling: Current status and future challenges.Redox biology · 2024Review
- FOXA2 Suppression by TRIM36 Exerts Anti-Tumor Role in Colorectal Cancer Via Inducing NRF2/GPX4-Regulated Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Battles against aberrant KEAP1-NRF2 signaling in lung cancer: intertwined metabolic and immune networks.Theranostics · 2023Review
- Review
- Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response.Molecules (Basel, Switzerland) · 2022Review
- Characterization of a small molecule inhibitor of disulfide reductases that induces oxidative stress and lethality in lung cancer cells.Cell reports · 2022Article
- Huoxiang Zhengqi alleviates azoxymethane/dextran sulfate sodium-induced colitis-associated cancer by regulating Nrf2/NF-κB/NLRP3 signaling.Frontiers in pharmacology · 2022Article
- The KEAP1-NRF2 System in Healthy Aging and Longevity.Antioxidants (Basel, Switzerland) · 2021Review
- Development of targeted therapy of NRF2Cellular signalling · 2021Review
- NRF2-Dependent Bioactivation of Mitomycin C as a Novel Strategy To Target KEAP1-NRF2 Pathway Activation in Human Cancer.Molecular and cellular biology · 2021Article
- c-MYC-directed NRF2 drives malignant progression of head and neck cancer via glucose-6-phosphate dehydrogenase and transketolase activation.Theranostics · 2021Article
- Enhancer remodeling promotes tumor-initiating activity in NRF2-activated non-small cell lung cancers.Nature communications · 2020Article
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
Aberrant activation of NRF2 is as a critical prognostic factor that drives the malignant progression of various cancers. Cancer cells with persistent NRF2 activation heavily rely on NRF2 activity for therapeutic resistance and aggressive tumorigenic capacity. To clarify the metabolic features of NRF2-activated lung cancers, we conducted targeted metabolomic (T-Met) and global metabolomic (G-Met) analyses of non-small-cell lung cancer (NSCLC) cell lines in combination with exome and transcriptome analyses. Exome analysis of 88 cell lines (49 adenocarcinoma, 14 large cell carcinoma, 15 squamous cell carcinoma and 10 others) identified non-synonymous mutations in the KEAP1, NRF2 and CUL3 genes. Judging from the elevated expression of NRF2 target genes, these mutations are expected to result in the constitutive stabilization of NRF2. Out of the 88 cell lines, 52 NSCLC cell lines (29 adenocarcinoma, 10 large cell carcinoma, 9 squamous cell carcinoma and 4 others) were subjected to T-Met analysis. Classification of the 52 cell lines into three groups according to the NRF2 target gene expression enabled us to draw typical metabolomic signatures induced by NRF2 activation. From the 52 cell lines, 18 NSCLC cell lines (14 adenocarcinoma, 2 large cell carcinoma, 1 squamous cell carcinoma and 1 others) were further chosen for G-Met and detailed transcriptome analyses. G-Met analysis of their culture supernatants revealed novel metabolites associated with NRF2 activity, which may be potential diagnostic biomarkers of NRF2 activation. This study also provides useful information for the exploration of new metabolic nodes for selective toxicity towards NRF2-activated NSCLC.
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