ArticlePloS one2015
Expression and functional role of orphan receptor GPR158 in prostate cancer growth and progression.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Transcriptional landscape of PTEN loss in primary prostate cancer.BMC cancer · 2021Pooled it
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- Additive effect of Bisphenol A and Pefluoro-sulphoctanoic acid exposure at subacute toxic levels, on a murine model of sertoli cell.Journal of endocrinological investigation · 2025Article
- G protein-coupled receptors in prostate cancer: research progress and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Legacy perfluoro-alkyl substances impair LDL-cholesterol uptake independently from PCSK9-function.Toxicology reports · 2023Article
- Expression Mapping and Functional Analysis of Orphan G-Protein-Coupled Receptor GPR158 in the Adult Mouse Brain Using a GPR158 Transgenic Mouse.Biomolecules · 2023Article
- Genomic Characterization of Prostatic Basal Cell Carcinoma.The American journal of pathology · 2023Article
- Review
- Effects of glutamate and aspartate on prostate cancer and breast cancer: a Mendelian randomization study.BMC genomics · 2022Article
- Cryo-EM structure of human GPR158 receptor coupled to the RGS7-Gβ5 signaling complex.Science (New York, N.Y.) · 2022Article
- The emerging roles of GPR158 in the regulation of the endocrine system.Frontiers in cell and developmental biology · 2022Review
- Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gβ5.Nature communications · 2021Article
- Insights into Nuclear G-Protein-Coupled Receptors as Therapeutic Targets in Non-Communicable Diseases.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Exposure to Perfluoro-Octanoic Acid Associated With Upstream Uncoupling of the Insulin Signaling in Human Hepatocyte Cell Line.Frontiers in endocrinology · 2021Article
- Whole-exome sequencing,American journal of cancer research · 2021Article
- Article
- An RNAi Screen for Genes Required for Growth ofG3 (Bethesda, Md.) · 2019Article
- Immunohistochemical validation of COL3A1, GPR158 and PITHD1 as prognostic biomarkers in early-stage ovarian carcinomas.BMC cancer · 2019Article
- GPR158 in the Visual System: Homeostatic Role in Regulation of Intraocular Pressure.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2019Article
- The putative G protein-coupled receptor GrlD mediates extracellular polyphosphate sensing in Dictyostelium discoideum.Molecular biology of the cell · 2019Article
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11 authors at 1 institution in 1 country.
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Abstract
Prostate cancer (PCa) is the second-leading cause of cancer-related mortality, after lung cancer, in men from developed countries. In its early stages, primary tumor growth is dependent on androgens, thus generally can be controlled by androgen deprivation therapy (ADT). Eventually however, the disease progresses to castration-resistant prostate cancer (CRPC), a lethal form in need of more effective treatments. G-protein coupled receptors (GPCRs) comprise a large clan of cell surface proteins that have been implicated as therapeutic targets in PCa growth and progression. The findings reported here provide intriguing evidence of a role for the newly characterized glutamate family member GPR158 in PCa growth and progression. We found that GPR158 promotes PCa cell proliferation independent of androgen receptor (AR) functionality and that this requires its localization in the nucleus of the cell. This suggests that GPR158 acts by mechanisms different from other GPCRs. GPR158 expression is stimulated by androgens and GPR158 stimulates AR expression, implying a potential to sensitize tumors to low androgen conditions during ADT via a positive feedback loop. Further, we found GPR158 expression correlates with a neuroendocrine (NE) differentiation phenotype and promotes anchorage-independent colony formation implying a role for GPR158 in therapeutic progression and tumor formation. GPR158 expression was increased at the invading front of prostate tumors that formed in the genetically defined conditional Pten knockout mouse model, and co-localized with elevated AR expression in the cell nucleus. Kaplan-Meier analysis on a dataset from the Memorial Sloan Kettering cancer genome portal showed that increased GPR158 expression in tumors is associated with lower disease-free survival. Our findings strongly suggest that pharmaceuticals targeting GPR158 activities could represent a novel and innovative approach to the prevention and management of CRPC.
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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.