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GENE:

LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)

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Other names: Leucine Rich Repeat Containing G Protein-Coupled Receptor 4, Leucine-Rich Repeat-Containing G-Protein Coupled Receptor 4, G Protein-Coupled Receptor 48, GPR48, G-Protein Coupled Receptor 48, BNMD17, LGR4
Associations
Trials
1m
Decoding adipocyte heterogeneity through single-nucleus transcriptomics unveils subtype-specific adipocytes orchestrate immunosuppressive niches in breast cancer. (PubMed, J Immunother Cancer)
This study delineated a distinct adipocyte landscape in breast cancer and subtype-specific immunosuppressive niches fostered by CAAs and (pre-) adipocyte-macrophage interactions. These findings provide novel therapeutic targets for microenvironment-directed interventions in breast oncology.
Journal
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ER (Estrogen receptor) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4) • TGFBR1 (Transforming Growth Factor Beta Receptor 1)
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ER positive
1m
RSPO4 exerts tumor suppression through antagonizing canonical and non-canonical Wnt signaling. (PubMed, Int J Biol Sci)
Mechanistically, RSPO4 exerted suppressive effects on Wnt signaling in an LGR4/5- and ZNRF3- dependent manner, through promoting LRP6 degradation and ZNRF3 stabilization. Our study revealed a novel role of RSPO4 as a tumor suppressor through antagonizing Wnt signaling, which provides important implications for development of diagnostic biomarkers and targeted therapy.
Journal
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RNF43 (Ring Finger Protein 43) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4) • RSPO1 (R-Spondin 1) • ZNRF3 (Zinc And Ring Finger 3)
3ms
Multi-omics analysis reveals that ALYREF-mediated m5C modification promotes platinum resistance in ovarian cancer via the NSUN2/ALYREF/LGR4 axis. (PubMed, Cell Death Dis)
In this study, we integrated RNA-Seq and single-cell transcriptomic data from cisplatin-resistant ovarian cancer cell lines and patient samples, identifying the m5C reader protein ALYREF as a key regulator of platinum resistance...Together, our findings demonstrate that the NSUN2/ALYREF/LGR4 axis mediates platinum resistance through m5C-dependent stabilization of LGR4 and downstream Wnt signaling activation. Thus, targeting ALYREF may represent a promising strategy to overcome platinum resistance in ovarian cancer.
Journal
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ALYREF (Aly/REF Export Factor) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)
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cisplatin
3ms
Construction and clinical validation of a machine-learning-based consensus prognostic signature (MLPS) for osteosarcoma via multi-cohort data integration. (PubMed, Int Immunopharmacol)
In vitro LGR4 knockdown significantly reduced osteosarcoma cell proliferation, migration, and PI3K-AKT-mTOR pathway activity, confirming its oncogenic role. These findings demonstrate the value of MLPS as a robust tool for prognostic assessment and individualized therapeutic decision-making in osteosarcoma.
Journal • IO biomarker
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LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)
4ms
ETV5 transcriptionally activates LGR4 and promotes cancer cell invasion and migration of nasopharyngeal carcinoma. (PubMed, J Mol Histol)
Our study revealed that ETV5 induces cell proliferation, invasion and migration by upregulating LGR4 in NPC. ETV5/LGR4 signaling may serve as a therapeutic target for NPC patients.
Journal
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ETV5 (ETS Variant Transcription Factor 5) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)
4ms
Leucine-rich repeat-containing G protein-coupled receptor 4 promotes proliferation, invasion and migration, and inhibits apoptosis in non-small cell lung cancer cells. (PubMed, Oncol Lett)
Moreover, GSEA indicated that elevated expression of LGR4 in NSCLC may trigger activation of critical signaling pathways, such as the Wnt/β-catenin, TGF-β and PI3K/AKT/mTOR pathways. Therefore, LGR4 could represent a promising biomarker and a potential target for therapy in the management of NSCLC.
Journal
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CTNNB1 (Catenin (cadherin-associated protein), beta 1) • TGFB1 (Transforming Growth Factor Beta 1) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)
5ms
Structural insights into Wnt/β-catenin signaling regulation by LGR4, R-spondin, and ZNRF3. (PubMed, Nat Commun)
This ternary arrangement and forced dimerization of ZNRF3 likely underpin how LGR4 and RSPO2 potentiate Wnt/β-catenin signaling by sequestering ZNRF3 from Wnt receptors and facilitating its auto-inactivation. This study provides a structural basis for understanding the regulatory mechanism of Wnt/β-catenin signaling through the LGR4-RSPO2-ZNRF3 pathway and may offer opportunities for future drug development targeting this axis.
Journal
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RSPO2 (R-Spondin 2) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4) • RSPO1 (R-Spondin 1) • ZNRF3 (Zinc And Ring Finger 3)
5ms
Journal
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STAT3 (Signal Transducer And Activator Of Transcription 3) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)
5ms
Identification of the Immune Microenvironment, Mutation Burden, Immunotherapy, and Drug Sensitivity Related to Lung Adenocarcinoma Tumor Stem Cells via WGCNA. (PubMed, Curr Cancer Drug Targets)
mRNAsi is associated with immunity, which was previously overlooked in the gene analysis of LUAD stem cells. These key genes have a strong overall corre-lation, which can be achieved by inhibiting the stemness characteristics of cancer cells, which may lay the foundation for future research on LUAD.
Journal • Tumor mutational burden • IO biomarker
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TMB (Tumor Mutational Burden) • PDGFB (Platelet Derived Growth Factor Subunit B) • PTTG1 (PTTG1 Regulator Of Sister Chromatid Separation, Securin) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)
6ms
RSPO2-based peptibodies conjugated with pyrrolobenzodiazepine dimer or camptothecin analogs demonstrate potent anti-tumor activity by targeting the three receptors LGR4/5/6. (PubMed, bioRxiv)
Peptibodies based on this RSPO2 furin mutant were conjugated with either pyrrolobenzodiazepine dimer or camptothecin derivative, and the resulting peptibodydrug conjugates (PDCs) showed potent and specific cytotoxic activity in neuroblastoma and colorectal cancer cell lines expressing any of LGR4/5/6 in vitro and robust anti-tumor activity in vivo. The results support the potential of RSPO2-based PDCs for the treatment of colorectal cancer, high-risk neuroblastoma, and other cancers that express LGR4/5/6.
Journal
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RSPO2 (R-Spondin 2) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)
6ms
Anti-tumor activity of camptothecin analog conjugate of an RSPO4-based peptibody targeting LGR4/5/6 in preclinical models of colorectal cancer. (PubMed, Br J Cancer)
Preclinical data showed that LGR4/5/6-targeting PDC exhibited potent cytotoxicity in vitro and robust antitumor efficacy in CRC xenograft and PDX models, making its potential as a promising therapeutic approach for CRC.
Preclinical • Journal
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LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4)
7ms
Exploring hepatic stellate cell-driven fibrosis: therapeutic advances and future perspectives. (PubMed, ADMET DMPK)
The review highlights critical research gaps in liver fibrosis therapy and promising active targeting strategies and pharmacological interventions to improve therapeutic outcomes. Overall, this review provides a robust foundation for scientists and clinicians to advance active targeting of the disease pathology and to develop new pharmaceutical formulations that are pharmacologically safer and more efficacious.
Review • Journal
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CTNNB1 (Catenin (cadherin-associated protein), beta 1) • RSPO3 (R-Spondin 3) • BSG (Basigin (Ok Blood Group)) • LGR4 (Leucine Rich Repeat Containing G Protein-Coupled Receptor 4) • TEAD4 (TEA Domain Transcription Factor 4)