ArticleStem cells (Dayton, Ohio)2013
Lgr4 is a key regulator of prostate development and prostate stem cell differentiation.
Article in Stem cells (Dayton, Ohio), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 66 citations in OpenAlex.
- Regulatory mechanisms of LGR4 on cancer and cancer stem cell properties.Discover oncology · 2026Review
- LGR4 promotes proliferation and homing via activation of the NF‑κB signaling pathway in multiple myeloma.International journal of oncology · 2025Article
- Unravelling the Mysteries of the Sonic Hedgehog Pathway in Cancer Stem Cells: Activity, Crosstalk and Regulation.Current issues in molecular biology · 2024Review
- BMP9 induces osteogenic differentiation through up-regulating LGR4 via the mTORC1/Stat3 pathway in mesenchymal stem cells.Genes & diseases · 2024Article
- Sensory innervation in the prostate and a role for calcitonin gene-related peptide in prostatic epithelial proliferation.Frontiers in molecular neuroscience · 2024Article
- YAP is required for prostate development, regeneration, and prostate stem cell function.Cell death discovery · 2023Article
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- Bioinformatics Analysis ofBiomolecules · 2022Article
- Exploring the Wnt Pathway as a Therapeutic Target for Prostate Cancer.Biomolecules · 2022Review
- LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation.Frontiers in endocrinology · 2022Review
- The role of R-spondin proteins in cancer biology.Oncogene · 2021Review
- The Role of LGR4 (GPR48) in Normal and Cancer Processes.International journal of molecular sciences · 2021Review
- Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis.Frontiers in genetics · 2021Review
- Stromal-AR influences the growth of epithelial cells in the development of benign prostate hyperplasia.Molecular and cellular biochemistry · 2020Article
- Regenerative potential of prostate luminal cells revealed by single-cell analysis.Science (New York, N.Y.) · 2020Article
- LGR4 overexpression is associated with clinical parameters and poor prognosis of serous ovarian cancer.Cancer biomarkers : section A of Disease markers · 2020Article
- miR-504 suppresses mesenchymal phenotype of glioblastoma by directly targeting the FZD7-mediated Wnt-β-catenin pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- Transcriptional Reprogramming and Novel Therapeutic Approaches for Targeting Prostate Cancer Stem Cells.Frontiers in oncology · 2019Review
- Unraveling the journey of cancer stem cells from origin to metastasis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Mechanisms modulating prostate cell fate determination remain unexplored. The leucine-rich repeat containing G-protein-coupled receptors (Lgr) have been identified as important stem cell markers in various tissues. Here, we investigated the roles of Lgr4/Gpr48 in prostate stem cells (PSCs) and development. Lgr4 was ubiquitously expressed during early prostate development prior to lineage specification, with adult expression restricted to a few basal cells (principally Lin(-)Sca1(+)CD49f(+)). Lgr4(-/-) mice had compromised branching morphogenesis and delayed epithelial differentiation, leading to decreased prostate size and impaired luminal cell function. In vitro prostate sphere culture revealed that Lgr4(-/-) Lin(-)/Sca1(+)/CD49f(+) cells failed to generate p63(low) cells, indicating a differentiation deficiency. Furthermore, Lgr4 ablation arrested PSC differentiation of in vivo kidney capsule prostate grafts, suggesting that Lgr4 modulates PSC properties independent of hormonal and mesenchymal effects. Analysis of neonatal prostates and prostate spheres revealed a decrease in Wnt, Sonic Hedgehog, and Notch1 expression in Lgr4(-/-) cells. Lgr4 loss blocked differentiation of prostate sphere p63(hi) cells to p63(low). Treatment with exogenous Sonic Hedgehog partially restored the differentiation of p63(hi) cells in Lgr4(-/-) spheres. Taken together, our data revealed the roles of Lgr4 in early prostate development and in stem cell differentiation through regulation of the Wnt, Notch, and Sonic Hedgehog signaling pathways.
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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.