ArticleThe EMBO journal2019
GSTZ1-1 Deficiency Activates NRF2/IGF1R Axis in HCC via Accumulation of Oncometabolite Succinylacetone.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 56 citations in OpenAlex.
- Metabolic Signatures for Liver Cancer Diagnosis and Mechanistic Insights: A Large-Scale, Multicenter Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- GSH-Related Enzymes GPx4, Chac1, and GSTs and Redox Regulation of Ferroptosis in Cancer.International journal of molecular sciences · 2026Review
- Targeting tRNA-dependent tyrosine usage unveils a metabolic vulnerability in hepatocellular carcinoma.Nature communications · 2026Article
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- Decoding amino acid metabolism in hepatocellular carcinoma: critical nodes and novel therapeutic strategy.Frontiers in oncology · 2026Review
- Harnessing ferroptosis for cancer therapy: Mechanisms and therapeutic strategies (Review).Oncology reports · 2026Review
- Prognostic modeling and immune infiltration analysis in hepatocellular carcinoma using glutathione metabolism-associated genes.European journal of medical research · 2025Article
- 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
- Amino acids shape the metabolic and immunologic landscape in the tumor immune microenvironment: from molecular mechanisms to therapeutic strategies.Cancer biology & medicine · 2025Review
- Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer.Cancer research · 2025Article
- AhR governs lipid metabolism: the role of gut microbiota.Frontiers in microbiology · 2025Review
- Ferroptosis: insight into the treatment of hepatocellular carcinoma.Cancer cell international · 2024Review
- HADH suppresses clear cell renal cell carcinoma progression through reduced NRF2-dependent glutathione synthesis.Translational oncology · 2024Article
- Amplifying colorectal cancer progression: impact of a PDIA4/SP1 positive feedback loop by circPDIA4 sponging miR-9-5p.Cancer biology & medicine · 2024Article
- Machine Learning and Experimental Validation Identified Ferroptosis Signature and Innovative Biomarkers (ESR1 and GSTZ1) in Liver Fibrosis.Journal of inflammation research · 2024Article
- Metabolome Profiling of Malignant Ascites Identifies Candidate Metabolic Biomarkers of Hepatocellular Carcinoma.Current medicinal chemistry · 2024Article
- Signaling metabolite succinylacetone activates HIF-1α and promotes angiogenesis in GSTZ1-deficient hepatocellular carcinoma.JCI insight · 2023Article
- Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.International journal of molecular sciences · 2023Review
- Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice.Nature communications · 2023Article
- Chemical Proteomics with Novel Fully Functionalized Fragments and Stringent Target Prioritization Identifies the Glutathione-Dependent Isomerase GSTZ1 as a Lung Cancer Target.ACS chemical biology · 2023Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
The IGF1R signaling is important in the malignant progression of cancer. However, overexpression of IGF1R has not been properly assessed in HCC. Here, we revealed that GSTZ1-1, the enzyme in phenylalanine/tyrosine catabolism, is downregulated in HCC, and its expression was negatively correlated with IGF1R. Mechanistically, GSTZ1-1 deficiency led to succinylacetone accumulation, alkylation modification of KEAP1, and NRF2 activation, thus promoting IGF1R transcription by recruiting SP1 to its promoter. Moreover, inhibition of IGF1R or NRF2 significantly inhibited tumor-promoting effects of GSTZ1 knockout in vivo. These findings establish succinylacetone as an oncometabolite, and GSTZ1-1 as an important tumor suppressor by inhibiting NRF2/IGF1R axis in HCC. Targeting NRF2 or IGF1R may be a promising treatment approach for this subset 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.