ArticleCell death & disease2023
A GSTP1-mediated lactic acid signaling promotes tumorigenesis through the PPP oxidative branch.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- A Systematic Review of Proteomics in Obesity: Unpacking the Molecular Puzzle.Current obesity reports · 2024Pooled it
- Adipocytes in cancer a metabolic paradox and the dawn of novel therapeutics.Discover oncology · 2026Review
- Mechanistic Insights Into Recurrent Implantation Failure: The Lactate-H3K18la-SLC7A11 Axis Explored via Endometrial Organoid and Blastoid-Endometrial Cell Implantation Models.Cell proliferation · 2026Article
- Integrated transcriptomics identifies HIF1A and GSTP1 as biomarkers for cutaneous squamous cell carcinoma.Translational cancer research · 2026Article
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- Mevalonate pathway in pancreatic ductal adenocarcinoma: Mechanisms driving metabolic and cellular plasticity.Cancer pathogenesis and therapy · 2026Review
- Regulation of Histone Emulsification by HPDL via LDHA/LDHB Promotes EC Cell Proliferation.Oncology research · 2026Article
- The lactate-lactylation axis in tumor radioresistance: metabolic, epigenetic, and immune mechanisms with emerging links to RNA regulation.Frontiers in immunology · 2026Review
- Lactate and lactylation in cancer: drivers of immune suppression and microenvironmental reprogramming.Experimental hematology & oncology · 2025Review
- Review
- [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
- A Mutual Interaction Between GSTP1 and p53 Improves the Drug Resistance and Malignant Biology of Pancreatic Cancer.Cancer science · 2025Article
- Aging and tumors: a dynamic interaction.Discover oncology · 2025Review
- GSTP1 knockdown induces metabolic changes affecting energy production and lipid balance in pancreatic cancer cells.Molecular & cellular oncology · 2025Article
- Glucose-6-phosphate dehydrogenase and its 3D structures from crystallography and electron cryo-microscopy.Acta crystallographica. Section F, Structural biology communications · 2024Review
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- Clinically relevant body composition phenotypes are associated with distinct circulating cytokine and metabolomic milieus in epithelial ovarian cancer patients.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lactic acidosis is a feature of solid tumors and plays fundamental role(s) rendering cancer cells to adapt to diverse metabolic stresses, but the mechanism underlying its roles in redox homeostasis remains elusive. Here we show that G6PD is phosphorylated at tyrosine 249/322 by the SRC through the formation of a GSTP1-G6PD-SRC complex. Lactic acid attenuates this formation and the phosphorylation of G6PD by non-covalently binding with GSTP1. Furthermore, lactic acid increases the activity of G6PD and facilitates the PPP (NADPH production) through its sensor GSTP1, thereby exhibiting resistance to reactive oxygen species when glucose is scarce. Abrogating a GSTP1-mediated lactic acid signaling showed attenuated tumor growth and reduced resistance to ROS in breast cancer cells. Importantly, positive correlations between immuno-enriched SRC protein and G6PD Y249/322 phosphorylation specifically manifest in ER/PR positive or HER negative types of breast cancer. Taken together, these results suggest that GSTP1 plays a key role in tumor development by functioning as a novel lactate sensor.
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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.