ArticleBMC cancer2023
Lactate receptor GPR81 drives breast cancer growth and invasiveness through regulation of ECM properties and Notch ligand DLL4.
Article in BMC cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 25 citations in OpenAlex.
- Interplay between N6-methyladenosine RNA methylation and protein lactylation: a novel crosstalk linking metabolism and epigenetic regulation in human diseases.Journal of translational medicine · 2026Review
- LINC01614 favors breast cancer progression through the regulation of miR-217/FN1 and mediation in PI3K/AKT signal pathway.Translational cancer research · 2026Article
- Beyond a waste product: lactate as a master metabolite dictating anti-tumor T-cell fate.Cell death & disease · 2026Review
- Metabolites as signalling molecules in the tumour immune microenvironment.Nature reviews. Immunology · 2026Review
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mechanisms and therapeutic implications of metabolic heterogeneity and histone lactylation in clear cell renal cell carcinoma.Discover oncology · 2026Review
- Lactate and lactylation: metabolic architects of tumor progression and metastasis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- A Machine Learning-Guided Approach for Identifying Potential HCAR1 Antagonists in Lactate-Driven Cancers.ACS omega · 2026Article
- Tumor suppressor gene chondroadherin opposes migration and proliferation in breast cancer and predicts a good survival.Discover oncology · 2026Article
- Immune-tumor cell ligand-receptor axes driving metabolic reprogramming and therapeutic resistance in cancer.Frontiers in immunology · 2026Review
- CircRNA circuits orchestrate lactate metabolism in gastrointestinal cancer progression.Open life sciences · 2026Article
- Functional and Mechanistic Insights of 3-Hydroxybutyrate (3-OBA) in Bladder Cancer.Molecules (Basel, Switzerland) · 2025Article
- 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
- GPR81 nuclear transportation is critical for cancer growth: Interaction of lactate receptor signaling and cell-extracellular matrix mechanotransduction.World journal of clinical oncology · 2025Article
- Lactate at the crossroads of tumor metabolism and immune escape: a new frontier in cancer therapy.Journal of translational medicine · 2025Review
- Lactylation modification in lung cancer: A review of current research and future directions (Review).Oncology reports · 2025Review
- GPR55 senses lactate to sustain motility in prostate cancer cells.Molecular and cellular biochemistry · 2025Article
- GPR81 nuclear transportation is critical for cancer growth and progression in lung and other solid cancers.World journal of clinical oncology · 2025Article
- Lactylation modifications in urological diseases: molecular mechanisms and biological implications.Clinical epigenetics · 2025Review
- Lactate and lactylation in breast cancer: current understanding and therapeutic opportunities.Cancer biology & medicine · 2025Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe lactate receptor GPR81 contributes to cancer development through unclear mechanisms. Here, we investigate the roles of GPR81 in three-dimensional (3D) and in vivo growth of breast cancer cells and study the molecular mechanisms involved.
methodsGPR81 was stably knocked down (KD) in MCF-7 human breast cancer cells which were subjected to RNA-seq analysis, 3D growth, in situ- and immunofluorescence analyses, and cell viability- and motility assays, combined with KD of key GPR81-regulated genes. Key findings were additionally studied in other breast cancer cell lines and in mammary epithelial cells.
resultsGPR81 was upregulated in multiple human cancer types and further upregulated by extracellular lactate and 3D growth in breast cancer spheroids. GPR81 KD increased spheroid necrosis, reduced invasion and in vivo tumor growth, and altered expression of genes related to GO/KEGG terms extracellular matrix, cell adhesion, and Notch signaling. Single cell in situ analysis of MCF-7 cells revealed that several GPR81-regulated genes were upregulated in the same cell clusters. Notch signaling, particularly the Notch ligand Delta-like-4 (DLL4), was strikingly downregulated upon GPR81 KD, and DLL4 KD elicited spheroid necrosis and inhibited invasion in a manner similar to GPR81 KD.
conclusionsGPR81 supports breast cancer aggressiveness, and in MCF-7 cells, this occurs at least in part via DLL4. Our findings reveal a new GPR81-driven mechanism in breast cancer and substantiate GPR81 as a promising treatment target.
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