ArticleScientific reports2015
Hypoxia-induced carbonic anhydrase IX facilitates lactate flux in human breast cancer cells by non-catalytic function.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 126 citations in OpenAlex.
- Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer.Current issues in molecular biology · 2026Review
- Intrinsic Asymmetry in Weak Acid Transmembrane Transporters.Biomolecules · 2026Review
- The pleiotropic roles of non-hormonal receptor basigin and regulatory microRNAs in breast cancer.NPJ breast cancer · 2025Review
- Article
- Design, synthesis,RSC advances · 2025Article
- CRISPRi/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity.Cell stem cell · 2024Article
- Targeting CA9 restricts pancreatic cancer progression through pH regulation and ROS production.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Disruption of the Physical Interaction Between Carbonic Anhydrase IX and the Monocarboxylate Transporter 4 Impacts Lactate Transport in Breast Cancer Cells.International journal of molecular sciences · 2024Article
- Lactate in breast cancer cells is associated with evasion of hypoxia-induced cell cycle arrest and adverse patient outcome.Human cell · 2024Article
- Article
- Differential carbonic anhydrase activities control EBV-induced B-cell transformation and lytic cycle reactivation.PLoS pathogens · 2024Article
- GHB toxicokinetics and renal monocarboxylate transporter expression are influenced by the estrus cycle in rats.BMC pharmacology & toxicology · 2023Article
- HIF: a master regulator of nutrient availability and metabolic cross-talk in the tumor microenvironment.The EMBO journal · 2023Review
- ADAM10 mediates shedding of carbonic anhydrase IX ectodomain non‑redundantly to ADAM17.Oncology reports · 2023Article
- Role of Human Monocarboxylate Transporter 1 (hMCT1) and 4 (hMCT4) in Tumor Cells and the Tumor Microenvironment.Cancer management and research · 2023Review
- Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies.Journal of enzyme inhibition and medicinal chemistry · 2022Review
- Local Attraction of Substrates and Co-Substrates Enhances Weak Acid and Base Transmembrane Transport.Biomolecules · 2022Review
- Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications.Journal of hematology & oncology · 2022Review
- Proton export upregulates aerobic glycolysis.BMC biology · 2022Article
- Cancer Therapeutic Targeting of Hypoxia Induced Carbonic Anhydrase IX: From Bench to Bedside.Cancers · 2022Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The most aggressive tumour cells, which often reside in hypoxic environments, rely on glycolysis for energy production. Thereby they release vast amounts of lactate and protons via monocarboxylate transporters (MCTs), which exacerbates extracellular acidification and supports the formation of a hostile environment. We have studied the mechanisms of regulated lactate transport in MCF-7 human breast cancer cells. Under hypoxia, expression of MCT1 and MCT4 remained unchanged, while expression of carbonic anhydrase IX (CAIX) was greatly enhanced. Our results show that CAIX augments MCT1 transport activity by a non-catalytic interaction. Mutation studies in Xenopus oocytes indicate that CAIX, via its intramolecular H(+)-shuttle His200, functions as a "proton-collecting/distributing antenna" to facilitate rapid lactate flux via MCT1. Knockdown of CAIX significantly reduced proliferation of cancer cells, suggesting that rapid efflux of lactate and H(+), as enhanced by CAIX, contributes to cancer cell survival under hypoxic conditions.
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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.