ArticleBiochimica et biophysica acta. Molecular and cell biology of lipids2020
GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cells.
Article in Biochimica et biophysica acta. Molecular and cell biology of lipids, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- GPR75 mediates hyperuricemia-induced endothelial inflammatory injury via a HOTAIR/miR-141-3p regulatory network.Molecular biology reports · 2026Article
- Blood multiomics reveal a dysregulated lipid mediator-mitochondrial network associated with the outcome of advanced cirrhosis.Nature communications · 2026Article
- Advancements in Understanding the Role of Oxylipins in Liver Injury and Liver Failure.Journal of clinical and translational hepatology · 2026Review
- GPR75 in glutamatergic neurons regulates body weight.Cell reports · 2026Article
- Anatomical and Neuronal Distribution of the G-Coupled Protein Receptor 75 mRNA in the Mouse Central Nervous System.The European journal of neuroscience · 2026Article
- On the interface of fatty acid metabolism: A crosstalk between fatty acid ω-hydroxylase CYP4F11 and fatty acid desaturase 2 in non-small cell lung cancer.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Brachyury and IGF1R: potential opposing roles in pediatric thyroid nodular pathology.Journal of endocrinological investigation · 2025Article
- Impacts of Oxylipins on ischemic stroke: from pathophysiology to clinical phenotypes.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- The curious family of cytochrome P450 4F fatty acid ω-hydroxylases: recent developments in their function and relevance for human health.Open biology · 2025Review
- GPR75: Advances, Challenges in Deorphanization, and Potential as a Novel Drug Target for Disease Treatment.International journal of molecular sciences · 2025Review
- The Use of Biologics for Targeting GPCRs in Metastatic Cancers.Biotech (Basel (Switzerland)) · 2025Review
- 20-HETE mediates Ang II-induced cardiac hypertrophy via ROS and CaScientific reports · 2025Article
- 20-Hydroxyeicosatetraenoic Acid Regulates the Src/EGFR/NF-κB Signaling Pathway Via GPR75 to Activate Microglia and Promote TBI in the Immature Brain.Neurochemical research · 2024Article
- Central regulation of feeding and body weight by ciliary GPR75.The Journal of clinical investigation · 2024Article
- Establishment of a neutrophil extracellular trap-related prognostic signature for colorectal cancer liver metastasis and expression validation of CYP4F3.Clinical and experimental medicine · 2024Article
- Review
- The CYP4/20-HETE/GPR75 axis in the progression metabolic dysfunction-associated steatosis liver disease (MASLD) to chronic liver disease.Frontiers in physiology · 2024Article
- Global and endothelial G-protein coupled receptor 75 (GPR75) knockout relaxes pulmonary artery and mitigates hypoxia-induced pulmonary hypertension.Vascular pharmacology · 2023Article
- Gpr75 knockout mice display age-dependent cone photoreceptor cell loss.Journal of neurochemistry · 2023Article
- Mice deficient for G-protein-coupled receptor 75 display altered presynaptic structural protein expression and disrupted fear conditioning recall.Journal of neurochemistry · 2023Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeRecent studies have shown that 20-hydroxyeicosatetraenoic acid (20-HETE) is a key molecule in sustaining androgen-mediated prostate cancer cell survival. Thus, the aim of this study was to determine whether 20-HETE can affect the metastatic potential of androgen-insensitive prostate cancer cells, and the implication of the newly described 20-HETE receptor, GPR75, in mediating these effects.
methodsThe expression of GPR75, protein phosphorylation, actin polymerization and protein distribution were assessed by western blot and/or fluorescence microscopy. Additionally, in vitro assays including epithelial-mesenchymal transition (EMT), metalloproteinase-2 (MMP-2) activity, scratch wound healing, transwell invasion and soft agar colony formation were used to evaluate the effects of 20-HETE agonists/antagonists or GPR75 gene silencing on the aggressive features of PC-3 cells.
results20-HETE (0.1 nM) promoted the acquisition of a mesenchymal phenotype by increasing EMT, the release of MMP-2, cell migration and invasion, actin stress fiber formation and anchorage-independent growth. Also, 20-HETE augmented the expression of HIC-5, the phosphorylation of EGFR, NF-κB, AKT and p-38 and the intracellular redistribution of p-AKT and PKCα. These effects were impaired by GPR75 antagonism and/or silencing. Accordingly, the inhibition of 20-HETE formation with N-hydroxy-N'-(4-n-butyl-2-methylphenyl) formamidine (HET0016) elicited the opposite effects.
conclusionsThe present results show for the first time the involvement of the 20-HETE-GPR75 receptor in the activation of intracellular signaling known to be stimulated in cell malignant transformations leading to the differentiation of PC-3 cells towards a more aggressive phenotype. Targeting the 20-HETE/GPR75 pathway is a promising and novel approach to interfere with prostate tumor cell malignant progression.
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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.