ArticleOncotarget2015
Hydroxycarboxylic acid receptors are essential for breast cancer cells to control their lipid/fatty acid metabolism.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Structures of G-protein coupled receptor HCAR3 in complex with selective agonists reveal the basis for ligand recognition and selectivity.PLoS biology · 2025Article
- Notch activity is modulated by the aGPCR Latrophilin binding the DSL ligand in C. elegans.Nature communications · 2025Article
- HCAR3 and Kynurenic Acid in Cancer: A Promising Axis of Immunometabolic Regulation or a Scientific Mirage?International journal of molecular sciences · 2025Review
- Unconventional receptor functions and location-biased signaling of the lactate GPCR in the nucleus.Life science alliance · 2025Article
- From metabolic reprogramming to epigenetic modification: association network and targeted treatment strategy between histone lactylation and tumor progression.Frontiers in immunology · 2025Review
- The Research Progress of Metformin Regulation of Metabolic Reprogramming in Malignant Tumors.Pharmaceutical research · 2024Review
- Assessment of Untargeted Metabolomics by Hydrophilic Interaction Liquid Chromatography-Mass Spectrometry to Define Breast Cancer Liquid Biopsy-Based Biomarkers in Plasma Samples.International journal of molecular sciences · 2024Article
- Dysfunction of the adhesion G protein-coupled receptor latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity.Signal transduction and targeted therapy · 2024Article
- Metformin increases 3-hydroxy medium chain fatty acids in patients with type 2 diabetes: a cross-sectional pharmacometabolomic study.Frontiers in endocrinology · 2024Article
- Signaling pathways in cancer metabolism: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Understanding the Contribution of Lactate Metabolism in Cancer Progress: A Perspective from Isomers.Cancers · 2022Review
- Lactate receptor HCAR1 regulates neurogenesis and microglia activation after neonatal hypoxia-ischemia.eLife · 2022Article
- Lactate receptor HCAR1 regulates cell growth, metastasis and maintenance of cancer‑specific energy metabolism in breast cancer cells.Molecular medicine reports · 2022Article
- Combining metabolic phenotype determination with metabolomics and transcriptional analyses to reveal pathways regulated by hydroxycarboxylic acid receptor 2.Discover oncology · 2022Article
- Tumor Microenvironment: Lactic Acid Promotes Tumor Development.Journal of immunology research · 2022Review
- Supplementation of ProbioticDiagnostics (Basel, Switzerland) · 2021Article
- Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases.BMC medical genomics · 2021Article
- Lactate Metabolism and Signaling in Tuberculosis and Cancer: A Comparative Review.Frontiers in cellular and infection microbiology · 2021Review
- Construction and Validation of an Immune-Related Gene Prognostic Index for Esophageal Squamous Cell Carcinoma.BioMed research international · 2021Article
- Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells exhibit characteristic changes in their metabolism with efforts being made to address them therapeutically. However, targeting metabolic enzymes as such is a major challenge due to their essentiality for normal proliferating cells. The most successful pharmaceutical targets are G protein-coupled receptors (GPCRs), with more than 40% of all currently available drugs acting through them.We show that, a family of metabolite-sensing GPCRs, the Hydroxycarboxylic acid receptor family (HCAs), is crucial for breast cancer cells to control their metabolism and proliferation.We found HCA1 and HCA3 mRNA expression were significantly increased in breast cancer patient samples and detectable in primary human breast cancer patient cells. Furthermore, siRNA mediated knock-down of HCA3 induced considerable breast cancer cell death as did knock-down of HCA1, although to a lesser extent. Liquid Chromatography Mass Spectrometry based analyses of breast cancer cell medium revealed a role for HCA3 in controlling intracellular lipid/fatty acid metabolism. The presence of etomoxir or perhexiline, both inhibitors of fatty acid β-oxidation rescues breast cancer cells with knocked-down HCA3 from cell death.Our data encourages the development of drugs acting on cancer-specific metabolite-sensing GPCRs as novel anti-proliferative agents for cancer therapy.
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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.