ArticleCancer letters2016
Lgr4 is crucial for skin carcinogenesis by regulating MEK/ERK and Wnt/β-catenin signaling pathways.
Article in Cancer letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Regulatory mechanisms of LGR4 on cancer and cancer stem cell properties.Discover oncology · 2026Review
- P2RY6 deletion promotes UVB-induced skin carcinogenesis by activating the PI3K/AKT signal pathway.Cancer science · 2025Article
- Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample.Cell · 2024Article
- Hepatic LGR4 aggravates cholestasis-induced liver injury in mice.American journal of physiology. Gastrointestinal and liver physiology · 2024Article
- Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/β-catenin signaling pathway.Gastroenterologia y hepatologia · 2024Article
- LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.Endocrine reviews · 2023Review
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- Exploring the Wnt Pathway as a Therapeutic Target for Prostate Cancer.Biomolecules · 2022Review
- 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
- Lgr4 Deletion Delays the Hair Cycle and Inhibits the Activation of Hair Follicle Stem Cells.The Journal of investigative dermatology · 2020Article
- LGR6 is a potential diagnostic and prognostic marker for esophageal squamous cell carcinoma.Journal of clinical laboratory analysis · 2020Article
- Nuclear-localized costimulatory molecule 4-1BBL promotes colon cancer cell proliferation and migration by regulating nuclear Gsk3β, and is linked to the poor outcomes associated with colon cancer.Cell cycle (Georgetown, Tex.) · 2020Article
- Pre-clinical evidences for the efficacy of tryptanthrin as a potent suppressor of skin cancer.Cell proliferation · 2020Article
- Silencing LGR6 Attenuates Stemness and Chemoresistance via Inhibiting Wnt/β-Catenin Signaling in Ovarian Cancer.Molecular therapy oncolytics · 2019Article
- Wnt Signaling Is a Major Determinant of Neuroblastoma Cell Lineages.Frontiers in molecular neuroscience · 2019Article
- Increased Immunoreactivity of LGR4 in Histologically Aggressive Basal Cell Carcinoma.Annals of dermatology · 2018Article
- LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Wnt Signalling Drives Context-Dependent Differentiation or Proliferation in Neuroblastoma.Neoplasia (New York, N.Y.) · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Lgr4 is a member of the leucine-rich, G protein-coupled receptor family of proteins, and has recently been shown to augment Wnt/β-catenin signaling via binding to Wnt agonists R-spondins. It plays an important role in skin development, but its involvement in skin tumorigenesis is unclear. Here, we report that mice deficient for Lgr4 are resistant to 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced keratinocyte proliferation and papilloma formation. We show that TPA treatment activates MEK1, ERK1/2 and downstream effector AP-1 in wild-type (WT) epidermal cells and mice, but not in cells or mice where Lgr4 is depleted. Wnt/β-catenin signaling is also dramatically activated by TPA treatment, and this activation is abolished when Lgr4 is deleted. We provide evidences that blocking both MEK1/ERK1/2 and Wnt/β-catenin pathways prevents TPA-induced increase in the expression of Ccnd1 (cyclin D1), a known Wnt/β-catenin target gene, and that the activation of MEK1/ERK1/2 pathway lies upstream of Wnt/β-catenin signal pathway. Collectively, our findings identify Lgr4 as a critical positive factor for skin tumorigenesis by mediating the activation of MEK1/ERK1/2 and Wnt/β-catenin pathways.
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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.