ArticleStem cells (Dayton, Ohio)2013
Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2.
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 61 papers.
What it found
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Who cites it
61 citing papers in PubMed, 93 citations in OpenAlex.
- Regulatory mechanisms of LGR4 on cancer and cancer stem cell properties.Discover oncology · 2026Review
- From lactation to malignancy: A comparison between healthy and cancerous breast gland at single-cell resolution reveals new issues for tumorigenesis.FEBS letters · 2025Article
- piRNAs as Potential Regulators of Mammary Gland Development and Pathology in Livestock.Veterinary sciences · 2025Review
- From unipotency to pluripotency: deciphering protein networks and signaling pathways in the generation of embryonic stem-like cells from murine spermatogonial stem cells.BMC genomics · 2025Article
- The frequency of known germline LGR4 missense variant in the ethnic groups of West Siberia.Molecular biology reports · 2024Article
- Unravelling the Mysteries of the Sonic Hedgehog Pathway in Cancer Stem Cells: Activity, Crosstalk and Regulation.Current issues in molecular biology · 2024Review
- RNF43 and ZNRF3 in Wnt Signaling - A Master Regulator at the Membrane.International journal of stem cells · 2023Review
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
- Validation of superior reference genes in mouse submandibular glands under developmental and functional regeneration states.International journal of molecular medicine · 2022Article
- LGR4, a G Protein-Coupled Receptor With a Systemic Role: From Development to Metabolic Regulation.Frontiers in endocrinology · 2022Review
- A Wnt-Independent LGR4-EGFR Signaling Axis in Cancer Metastasis.Cancer research · 2021Article
- The Role of LGR4 (GPR48) in Normal and Cancer Processes.International journal of molecular sciences · 2021Review
- Prolactin synergizes with canonical Wnt signals to drive development of ER+ mammary tumors via activation of the Notch pathway.Cancer letters · 2021Article
- Emerging Roles for LGR4 in Organ Development, Energy Metabolism and Carcinogenesis.Frontiers in genetics · 2021Review
- Intertwined Signaling Pathways Governing Tooth Development: A Give-and-Take Between Canonical Wnt and Shh.Frontiers in cell and developmental biology · 2021Review
- Article
- Intraductal Injection of Lentivirus Vectors for Stably Introducing Genes into Rat Mammary Epithelial Cells in Vivo.Journal of mammary gland biology and neoplasia · 2020Article
- Two Sides of the Same Coin: The Role of Developmental pathways and pluripotency factors in normal mammary stem cells and breast cancer metastasis.Journal of mammary gland biology and neoplasia · 2020Review
- Circular RNAs and their participation in stemness of cancer.Medical oncology (Northwood, London, England) · 2020Review
- Progesterone and Breast Cancer.Endocrine reviews · 2020Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The key signaling networks regulating mammary stem cells are poorly defined. The leucine-rich repeat containing G protein-coupled receptor (Lgr) family has been implicated in intestinal, gastric, and epidermal stem cell functions. We investigated whether Lgr4 functions in mammary gland development and mammary stem cells. We found that Lgr4(-/-) mice had delayed ductal development, fewer terminal end buds, and decreased side-branching. Crucially, the mammary stem cell repopulation capacity was severely impaired. Mammospheres from Lgr4(-/-) mice showed decreased Wnt signaling. Wnt3a treatment prevented the adverse effects of Lgr4 loss on organoid formation. Chromatin immunoprecipitation analysis indicated that Sox2 expression was controlled by the Lgr4/Wnt/β-catenin/Lef1 pathway. Importantly, Sox2 overexpression restored the in vivo mammary regeneration potential of Lgr4(-/-) mammary stem cells. Therefore, Lgr4 activates Sox2 to regulate mammary development and stem cell functions via Wnt/β-catenin/Lef1.
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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.