ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Targeting GSTP1 as Therapeutic Strategy against Lung Adenocarcinoma Stemness and Resistance to Tyrosine Kinase Inhibitors.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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, 34 citations in OpenAlex.
- Transcriptional activation of GSTP1 by ANXA3 is associated with cisplatin sensitivity in colorectal cancer cells.Oncology letters · 2026Article
- 6PPDQ Promotes Cutaneous Squamous Cell Carcinoma Growth with PI3K-Akt/MMP9 Activation: Evidence from Integrated Network Toxicology and Experimental Investigation.International journal of molecular sciences · 2026Article
- Integrated transcriptomics identifies HIF1A and GSTP1 as biomarkers for cutaneous squamous cell carcinoma.Translational cancer research · 2026Article
- Single-cell insights into cisplatin resistance mechanisms in bladder cancer tumor microenvironment.The Journal of biological chemistry · 2026Article
- sc-rDSeq: a robust and cost-effective full-length total RNA sequencing method for single cells reveals multilayered heterogeneity in drug-resistant lung cancer cells.Nucleic acids research · 2026Article
- WTAP-mediated m6A methylation of SOX2 affects lung adenocarcinoma malignancy via Wnt/β-catenin pathway.Frontiers in genetics · 2026Article
- Targeting the exosomal CaMK2A-ZDHHC3-GPX4 pathway reprograms tumor-associated macrophages and enhances anti-PD-1/PD-L1 immunotherapy in gastric cancer.International journal of biological sciences · 2026Article
- Verapamil Reduces Collagen Synthesis to Alleviate Ureteral Scar Formation by Inhibiting KDM1A-Mediated Epigenetic Silencing of SESN2.Kidney & blood pressure research · 2026Article
- Targeting the miR-325-3p/GSTP1 axis overcomes paclitaxel resistance in triple-negative breast cancer by inducing ferroptosis.Genes & genomics · 2025Article
- IGF2BP1-mediated methylation of ABCA1 facilitates tumor progression by affecting cholesterol metabolism in lung adenocarcinoma.Amino acids · 2025Article
- [Multi-omics analysis of the relationship between oxidative stress-related gene and prostate cancer].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- The effect of the combination therapy with chlorophyllin, a glutathione transferase P1-1 inhibitor, and docetaxel on triple-negative breast cancer invasion and metastasis in vivo/in vitro.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
- METTL3 inhibits primed-to-naïve transition of pluripotent stem cells through mCell regeneration (London, England) · 2025Article
- A Mutual Interaction Between GSTP1 and p53 Improves the Drug Resistance and Malignant Biology of Pancreatic Cancer.Cancer science · 2025Article
- Dual-specificity phosphatase 23 functions as a promising prognostic biomarker in non-small cell lung cancer.Genes & genomics · 2025Article
- Lung cancer organoids: a new strategy for precision medicine research.Translational lung cancer research · 2025Review
- Integrated multi-omics analysis and experimental investigation of mitochondrial dynamics-related genes: molecular subtypes, immune landscape, and prognostic implications in lung adenocarcinoma.Frontiers in immunology · 2025Article
- GSTP1 improves CAR-T cell proliferation and cytotoxicity to combat lymphoma.Frontiers in immunology · 2025Article
- Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Glutathione S-transferase pi (GSTP1), a phase II detoxification enzyme, is known to be overexpressed and mediates chemotherapeutic resistance in lung cancer. However, whether GSTP1 supports cancer stem cells (CSCs) and the underlying mechanisms in lung adenocarcinoma (LUAD) remain largely unknown. This study unveiled that GSTP1 is upregulated in lung CSCs and supports tumor self-renewal, metastasis, and resistance to targeted tyrosine kinase inhibitors of LUAD both in vitro and in vivo. Mechanistically, CaMK2A (calcium/calmodulin-dependent protein kinase 2 isoform A)/NRF2 (nuclear factor erythroid 2-related factor 2)/GSTP1 is uncovered as a regulatory axis under hypoxia. CaMK2A increased GSTP1 expression through phosphorylating the Sersine558 residue of NRF2 and promoting its nuclear translocation, a novel mechanism for NRF2 activation apart from conventional oxidization-dependent activation. Upregulation of GSTP1 in turn suppressed reactive oxygen species levels and supported CSC phenotypes. Clinically, GSTP1 analyzed by immunohistochemistry is upregulated in a proportion of LUAD and serves as a prognostic marker for survival. Using patient-derived organoids from an ALK-translocated LUAD, the therapeutic potential of a specific GSTP1 inhibitor ezatiostat in combination treatment with the ALK inhibitor crizotinib is demonstrated. This study demonstrates GSTP1 to be a promising therapeutic target for long-term control of LUAD through targeting CSCs.
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