ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2018
LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Array expression meta-analysis of cancer stem cell genes identifies upregulation of PODXL especially in DCC low expression meningiomas.PloS one · 2019Pooled it
- Runx1 and Runx2 act in concert to suppress Wnt/β-catenin-driven mammary tumourigenesis.British journal of cancer · 2026Article
- Regulatory mechanisms of LGR4 on cancer and cancer stem cell properties.Discover oncology · 2026Review
- Review
- Ferroptosis contributes to quercetin-induced anti-cancer activity through blockade of LGR4/NF-κB/GPX4 axis in oral squamous cell carcinoma.Frontiers in oncology · 2026Article
- Leucine-rich repeat-containing G protein-coupled receptor 4 promotes proliferation, invasion and migration, and inhibits apoptosis in non-small cell lung cancer cells.Oncology letters · 2025Article
- LILRB4 regulates circadian disruption-induced mammary tumorigenesis via non-canonical WNT signaling pathway.Oncogene · 2025Article
- Anti-tumor activity of camptothecin analog conjugate of an RSPO4-based peptibody targeting LGR4/5/6 in preclinical models of colorectal cancer.British journal of cancer · 2025Article
- The Use of Biologics for Targeting GPCRs in Metastatic Cancers.Biotech (Basel (Switzerland)) · 2025Review
- Regulation of RSPO3-LGR4 Signaling: Emerging Role in Inflammation Revealed by Network Analysis.Archives of clinical and biomedical research · 2025Article
- The role of LGR4 in bone metabolism and tumor bone metastasis.Frontiers in endocrinology · 2025Review
- The frequency of known germline LGR4 missense variant in the ethnic groups of West Siberia.Molecular biology reports · 2024Article
- Baicalein inhibits cell proliferation and induces apoptosis in brain glioma cells by downregulating the LGR4-EGFR pathway.Cancer gene therapy · 2024Article
- Identification of an immune-related genes signature in lung adenocarcinoma to predict survival and response to immune checkpoint inhibitors.Journal of the Egyptian National Cancer Institute · 2024Article
- Development of a TLR-Based Model That Can Predict Prognosis, Tumor Microenvironment, and Drug Response for Esophageal Squamous Cell Carcinoma.Biochemical genetics · 2024Article
- The antifibrotic potential of IMT504: modulation of GLAST + Wnt1 + bone marrow stromal progenitors and hepatic microenvironment.Stem cell research & therapy · 2024Article
- Wnt signaling and tumors (Review).Molecular and clinical oncology · 2024Review
- Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/β-catenin signaling pathway.Gastroenterologia y hepatologia · 2024Article
- LGR4 attenuates MGP expression and suppresses EGFR activation-induced triple-negative breast cancer metastasis.American journal of cancer research · 2024Article
- Oncoinformatic screening of the gene clusters involved in the HER2-positive breast cancer formation along with the in silico pharmacodynamic profiling of selective long-chain omega-3 fatty acids as the metastatic antagonists.Molecular diversity · 2023Article
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
Abstract
The fourth member of the leucine-rich repeat-containing GPCR family (LGR4, frequently referred to as GPR48) and its cognate ligands, R-spondins (RSPOs) play crucial roles in the development of multiple organs as well as the survival of adult stem cells by activation of canonical Wnt signaling. Wnt/β-catenin signaling acts to regulate breast cancer; however, the molecular mechanisms determining its spatiotemporal regulation are largely unknown. In this study, we identified LGR4 as a master controller of Wnt/β-catenin signaling-mediated breast cancer tumorigenesis, metastasis, and cancer stem cell (CSC) maintenance. LGR4 expression in breast tumors correlated with poor prognosis. Either Lgr4 haploinsufficiency or mammary-specific deletion inhibited mouse mammary tumor virus (MMTV)- PyMT- and MMTV- Wnt1-driven mammary tumorigenesis and metastasis. Moreover, LGR4 down-regulation decreased in vitro migration and in vivo xenograft tumor growth and lung metastasis. Furthermore, Lgr4 deletion in MMTV- Wnt1 tumor cells or knockdown in human breast cancer cells decreased the number of functional CSCs by ∼90%. Canonical Wnt signaling was impaired in LGR4-deficient breast cancer cells, and LGR4 knockdown resulted in increased E-cadherin and decreased expression of N-cadherin and snail transcription factor -2 ( SNAI2) (also called SLUG), implicating LGR4 in regulation of epithelial-mesenchymal transition. Our findings support a crucial role of the Wnt signaling component LGR4 in breast cancer initiation, metastasis, and breast CSCs.-Yue, Z., Yuan, Z., Zeng, L., Wang, Y., Lai, L., Li, J., Sun, P., Xue, X., Qi, J., Yang, Z., Zheng, Y., Fang, Y., Li, D., Siwko, S., Li, Y., Luo, J., Liu, M. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.
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