ArticleMolecular cancer therapeutics2023
A Carbonic Anhydrase IX/SLC1A5 Axis Regulates Glutamine Metabolism Dependent Ferroptosis in Hypoxic Tumor Cells.
Article in Molecular cancer therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Unveiling the Gut-Brain Axis: Fusobacteriaceae Promotes Parkinson's Disease Development via CA9 Suppression-Induced Ferroptosis.Journal of molecular neuroscience : MN · 2026Article
- Carbonic Anhydrase Inhibitors in Oncology.Sub-cellular biochemistry · 2026Review
- Ferroptosis and renal fibrosis: mechanistic insights and emerging therapeutic targets.Renal failure · 2025Review
- Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.Experimental hematology & oncology · 2025Review
- Targeting carbonic anhydrase IX/XII prevents the anti-ferroptotic effect of stromal lactic acid in prostate carcinoma.Molecular oncology · 2025Article
- Overexpression of the ferroptosis-related gene, NFS1, corresponds to gastric cancer growth and tumor immune infiltration.Open life sciences · 2025Article
- IL-1β promotes glutamate excitotoxicity: indications for the link between inflammatory and synaptic vesicle cycle in Ménière's disease.Cell death discovery · 2024Article
- Exploring the Polypharmacological Potential of PCI-27483: A Selective Inhibitor of Carbonic Anhydrases IX and XII.ACS medicinal chemistry letters · 2024Article
- From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- Enhancing Colorectal Cancer Immunotherapy: The Pivotal Role of Ferroptosis in Modulating the Tumor Microenvironment.International journal of molecular sciences · 2024Review
- Synthesis and Enzymatic Evaluation of a Small Library of Substituted Phenylsulfonamido-Alkyl Sulfamates towards Carbonic Anhydrase II.Molecules (Basel, Switzerland) · 2024Article
- Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.Molecular metabolism · 2024Review
- Carbonic Anhydrase Inhibitors Induce Ferroptosis through Inhibition of AKT/FTH1 Signaling in Ewing Sarcoma Tumor Cells.Cancers · 2023Article
- The Regulation of Ferroptosis by Noncoding RNAs.International journal of molecular sciences · 2023Review
- Co-vulnerabilities of inhibiting carbonic anhydrase IX in ferroptosis-mediated tumor cell death.Frontiers in molecular biosciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The ability of tumor cells to alter their metabolism to support survival and growth presents a challenge to effectively treat cancers. Carbonic anhydrase IX (CAIX) is a hypoxia-induced, metabolic enzyme that plays a crucial role in pH regulation in tumor cells. Recently, through a synthetic lethal screen, we identified CAIX to play an important role in redox homeostasis. In this study, we show that CAIX interacts with the glutamine (Gln) transporter, solute carrier family 1 member 5 (SLC1A5), and coordinately functions to maintain redox homeostasis through the glutathione/glutathione peroxidase 4 (GSH/GPX4) axis. Inhibition of CAIX increases Gln uptake by SLC1A5 and concomitantly increases GSH levels. The combined inhibition of CAIX activity and Gln metabolism or the GSH/GPX4 axis results in an increase in lipid peroxidation and induces ferroptosis, both in vitro and in vivo. Thus, this study demonstrates cotargeting of CAIX and Gln metabolism as a potential strategy to induce ferroptosis in tumor cells.
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Registered trials
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