ArticleJournal of experimental & clinical cancer research : CR2019
GSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Insight into Nrf2: a bibliometric and visual analysis from 2000 to 2022.Frontiers in genetics · 2023Pooled it
- Targeting GSTZ1 Sensitizes KRASG12C-Mutant Lung Cancer Cells by Overcoming Glutathione and Glycolysis Pathway Rewiring.Cancer research communications · 2026Article
- Genetic associations with longevity in a Calabrian cohort: an exploratory genome-wide study.GeroScience · 2026Article
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- Prognostic modeling and immune infiltration analysis in hepatocellular carcinoma using glutathione metabolism-associated genes.European journal of medical research · 2025Article
- Reproducible autosomal gene expression changes with loss of typical X and Y complement across tumor types.bioRxiv : the preprint server for biology · 2025Article
- Variants inGenes · 2025Review
- Adipose-derived mesenchymal stem cell-derived extracellular vesicles carry microRNA-214-3p to target GSTZ1 to curb ferroptosis in lung epithelial cells during sepsis.Cytotechnology · 2025Article
- A new opportunity for N-acetylcysteine. An outline of its classic antioxidant effects and its pharmacological potential as an epigenetic modulator in liver diseases treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The Role of Redox Environment in Tumors.Current medicinal chemistry · 2025Review
- Ferroptosis: insight into the treatment of hepatocellular carcinoma.Cancer cell international · 2024Review
- Transcriptomic Profiling for Prognostic Biomarkers in Early-Stage Squamous Cell Lung Cancer (SqCLC).Cancers · 2024Article
- Exploration of a hypoxia-immune-related microenvironment gene signature and prediction model for hepatitis C-induced early-stage fibrosis.Journal of translational medicine · 2024Article
- Machine Learning and Experimental Validation Identified Ferroptosis Signature and Innovative Biomarkers (ESR1 and GSTZ1) in Liver Fibrosis.Journal of inflammation research · 2024Article
- Dual role of Nrf2 signaling in hepatocellular carcinoma: promoting development, immune evasion, and therapeutic challenges.Frontiers in immunology · 2024Review
- Roles and Mechanisms of Ferroptosis in Sorafenib Resistance for Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- Exploring the application of dietary antioxidant index for disease risk assessment: a comprehensive review.Frontiers in nutrition · 2024Review
- Article
- Signaling metabolite succinylacetone activates HIF-1α and promotes angiogenesis in GSTZ1-deficient hepatocellular carcinoma.JCI insight · 2023Article
- Antioxidant and Anti-Tumor Effects of Dietary Vitamins A, C, and E.Antioxidants (Basel, Switzerland) · 2023Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundGlutathione S-transferase zeta 1 (GSTZ1) is the penultimate enzyme in phenylalanine/tyrosine catabolism. GSTZ1 is dysregulated in cancers; however, its role in tumorigenesis and progression of hepatocellular carcinoma (HCC) is largely unknown. We aimed to assess the role of GSTZ1 in HCC and to reveal the underlying mechanisms, which may contribute to finding a potential therapeutic strategy against HCC.
methodsWe first analyzed GSTZ1 expression levels in paired human HCC and adjacent normal tissue specimens and the prognostic effect of GSTZ1 on HCC patients. Thereafter, we evaluated the role of GSTZ1 in aerobic glycolysis in HCC cells on the basis of the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Furthermore, we assessed the effect of GSTZ1 on HCC proliferation, glutathione (GSH) concentration, levels of reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor 2 (NRF2) signaling via gain- and loss- of GSTZ1 function in vitro. Moreover, we investigated the effect of GSTZ1 on diethylnitrosamine (DEN) and carbon tetrachloride (CCl
resultsGSTZ1 was downregulated in HCC, thus indicating a poor prognosis. GSTZ1 deficiency significantly promoted hepatoma cell proliferation and aerobic glycolysis in HCC cells. Moreover, loss of GSTZ1 function depleted GSH, increased ROS levels, and enhanced lipid peroxidation, thus activating the NRF2-mediated antioxidant pathway. Furthermore, Gstz1 knockout in mice promoted DEN/CCl
conclusionsGSTZ1 serves as a tumor suppressor in HCC. GSH depletion caused by GSTZ1 deficiency elevates oxidative stress, thus constitutively activating the NRF2 antioxidant response pathway and accelerating HCC progression. Targeting the NRF2 signaling pathway may be a promising therapeutic approach for this subset of HCC.
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Registered trials
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.