ArticleAntioxidants (Basel, Switzerland)2022
The Crosstalk between GPR81/IGFBP6 Promotes Breast Cancer Progression by Modulating Lactate Metabolism and Oxidative Stress.
Article in Antioxidants (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 48 citations in OpenAlex.
- GPR81 Regulates MCT1 Membrane Translocation Through a PKA-Dependent Signaling Pathway in Rat Podocytes.International journal of molecular sciences · 2026Article
- Lysine lactylation-mediated post-translational modification: Molecular mechanisms and therapeutic target exploration in tumour drug resistance.Clinical and translational medicine · 2026Review
- Targeting histamine H4 receptor improves anti-tumoral response in a murine model of breast cancer.Frontiers in immunology · 2026Article
- The Impact of IGFBP6 Knockdown on Cholesterol Metabolism in Breast Cancer Cells.Current medicinal chemistry · 2026Article
- GPCRs as key regulators in wound healing.Frontiers in cell and developmental biology · 2026Review
- The Emerging Roles of Metabolite-Activated GPCRs in Teleost Physiology and Aquaculture Development.Metabolites · 2025Review
- Lactate-mediated activation of GPR81 regulates BCR/Abl protein expression in chronic myeloid leukemia cells selected under low oxygen tension.The Journal of pathology · 2025Article
- Lactylation in cancer biology: Unlocking new avenues for research and therapy.Cancer communications (London, England) · 2025Review
- Lactate and lactylation in cancer: drivers of immune suppression and microenvironmental reprogramming.Experimental hematology & oncology · 2025Review
- Lactate and lactylation in tumor immunity.Frontiers of medicine · 2025Review
- Nanozyme eye drops for retinal barrier penetration and vasculopathy repair.Science advances · 2025Article
- LMO7 drives profibrotic fibroblast polarization and pulmonary fibrosis in mice through TGF-β signalling.Acta pharmacologica Sinica · 2025Article
- Redox Biology and Insulin-like Growth Factor-Binding Protein-6: A Potential Relationship.Biology · 2025Review
- Correction: Longhitano et al. The Crosstalk between GPR81/IGFBP6 Promotes Breast Cancer Progression by Modulating Lactate Metabolism and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Article
- Alveolar epithelial type 2 cell specific loss of IGFBP2 activates inflammation in COVID-19.Respiratory research · 2025Article
- Insulin-like growth factor family and its impact on pulmonary arterial hypertension: a review.Frontiers in physiology · 2025Review
- Single-Cell View of Tumor Microenvironment Gradients in Pleural Mesothelioma.Cancer discovery · 2024Article
- Regulatory roles of insulin growth factor binding protein family in neuroblastoma cell proliferation and differentiation: Potential prognostic biomarkers and therapeutic targets for neuroblastoma.Pediatric discovery · 2024Review
- Non-dialyzable uremic toxins and renal tubular cell damage in CKD patients: a systems biology approach.European journal of medical research · 2024Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is the most frequent tumor and the leading cause of cancer deaths in women. In recent years, lactate metabolism and, in particular, its receptor GPR81 have been shown to play a vital role in cancer biology. GPR81 is upregulated in breast cancer and promotes tumor growth by tumor cell-derived lactate. Therefore, the search for possible crosstalk and the involvement of new molecules capable of generating this pathology is always in continuous development. In this study, the relationship between GPR81 and IGFBP6 protein in tumor growth and oxidative stress in the human breast cancer cell line MDA-MB-231 was studied. Cells were treated with lactate or the GPR81 receptor agonist and antagonist 3,5-DHBA and 3-OBA, respectively. In addition, oxidative stress and proliferation were also evaluated in cells challenged with the recombinant IGFBP6 protein. Our data showed that lactate induced cell proliferation and wound healing of the MDA-231 breast cancer cell through the overexpression of both the lactate receptor GPR81 and IGFBP6. The increase in IGFBP6 was able, in turn, to improve the mitochondrial fitness and redox state, as suggested by the reduced levels of mitochondrial ROS production after IGFBP6 treatment, presumably mediated by the increase in the ROS detoxifying genes HMOX1, GSTK1 and NQO1. In conclusion, our data highlight a novel axis between GPR81 and IGFBP6 in MDA-231 cells able to modulate lactate metabolism and oxidative stress. This complex signaling may represent a new therapeutic target for breast cancer.
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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.