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MetabolomicsTargeting GSTZ1 sensitizes KRASG12C-mutant lung cancer cells by overcoming glutathione and glycolysis pathway rewiring

KRAS mutations are prevalent in lung cancer, but KRAS G12C inhibitors exhibit limited efficacy, partly due to metabolic adaptations, such as enhanced glutathione metabolism and increased glycolysis. Glutathione S-Transferase Zeta 1 (GSTZ1) is a metabolic enzyme that regulates cell metabolism. How...

2026-05-15 | MTBLS12791 | MetaboLights
ProteomicsChemical proteomics with novel fully functionalized fragments and stringent target prioritization identifies the glutathione-dependent isomerase GSTZ1 as a lung cancer target: SuTEx of GSTZ1 KD
Photoreactive fragment-like probes have been applied to discover target proteins that constitute novel cellular vulnerabilities and to identify viable chemical hits for drug discovery. Through forming covalent bonds, functionalized probes can achieve stronger target engagement and require less effor...
ORGANISM(S): Homo sapiens (Human) 
2024-04-05 | PXD037894 | Pride
Fragment-based drug discovery Gstz1 Lung cancer Chemical proteomics 
GenomicsOncometabolite succinylacetone activates HIF-1α signaling and promotes angiogenesis in GSTZ1-deficient HCC
Oncometabolite succinylacetone activates HIF-1α signaling and promotes angiogenesis in GSTZ1-deficient HCC
PRJNA793036 | ENA
ProteomicsChemical proteomics with novel fully functionalized fragments and stringent target prioritization identifies the glutathione-dependent isomerase GSTZ1 as a lung cancer target
Photoreactive fragment-like probes have been applied to discover target proteins that constitute novel cellular vulnerabilities and to identify viable chemical hits for drug discovery. Through forming covalent bonds, functionalized probes can achieve stronger target engagement and require less effor...
ORGANISM(S): Homo sapiens (Human) 
2024-04-05 | PXD035201 | Pride
Photoreactive probes Lung cancer Gstz1 Chemical proteomics 
UnknownThe influence of human GSTZ1 gene haplotype variations on GSTZ1 expression.
Not available
S-EPMC4382440 | biostudies-literature
TranscriptomicsOncometabolite succinylacetone activates HIF-1α signaling and promotes angiogenesis in GSTZ1-deficient HCC
We describe a unique regulation of the succinylacetone/PHD2/HIF-1α axis by a metabolic enzyme GSTZ1. The total RNA was isolated from HepG2 cells stably transfected with or without GSTZ1-KO and analyzed using RNA-seq. Our work demonstrates that GSTZ1-deficient promotes HCC angiogenesis through stabil...
ORGANISM(S): Homo sapiens 
2023-11-06 | GSE192760 | GEO
UnknownGSTZ1 deficiency promotes hepatocellular carcinoma proliferation via activation of the KEAP1/NRF2 pathway.
Not available
S-EPMC6822483 | biostudies-literature
UnknownAge-Related Changes in miRNA Expression Influence GSTZ1 and Other Drug Metabolizing Enzymes.
Not available
S-EPMC7289049 | biostudies-literature
UnknownGSTZ1-1 downregulates Wnt/β-catenin signalling in hepatocellular carcinoma cells.
Not available
S-EPMC6943223 | biostudies-literature
UnknownGSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis.
Not available
S-EPMC8087704 | biostudies-literature
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