ArticleCell death and differentiation2016
Merlin inhibits Wnt/β-catenin signaling by blocking LRP6 phosphorylation.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- The Wnt signaling networks in higher-grade meningiomas: from molecular pathogenesis to therapeutic innovation.Cancer cell international · 2026Review
- Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets.Biomolecules · 2025Review
- Current molecular understanding of central nervous system schwannomas.Acta neuropathologica communications · 2025Review
- MerlinNature communications · 2024Article
- NF2 regulates IP3R-mediated CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- The molecular biology of NF2/Merlin on tumorigenesis and development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- A PAK family kinase and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Retinoic acid induced specific changes in the phosphoproteome of C17.2 neural stem cells.Journal of cellular and molecular medicine · 2024Article
- The genetic landscape and possible therapeutics of neurofibromatosis type 2.Cancer cell international · 2023Review
- CCN3/NOV promotes metastasis and tumor progression via GPNMB-induced EGFR activation in triple-negative breast cancer.Cell death & disease · 2023Article
- Article
- Celastrol suppresses the growth of vestibular schwannoma in mice by promoting the degradation of β-catenin.Acta pharmacologica Sinica · 2022Article
- PI(4,5)PScience signaling · 2022Article
- Review
- In Vivo Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma.Cancer research · 2022Article
- Integrative analysis of hub genes and key pathway in two subtypes of diffuse large B-cell lymphoma by bioinformatics and basic experiments.Journal of clinical laboratory analysis · 2021Article
- Wnt/β-catenin signaling: Structure, assembly and endocytosis of the signalosome.Development, growth & differentiation · 2021Review
- Article
- Regulation of the Low-Density Lipoprotein Receptor-Related Protein LRP6 and Its Association With Disease: Wnt/β-Catenin Signaling and Beyond.Frontiers in cell and developmental biology · 2021Review
- Nf2 fine-tunes proliferation and tissue alignment during closure of the optic fissure in the embryonic mouse eye.Human molecular genetics · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Merlin, encoded by the NF2 gene, is a tumor suppressor that acts by inhibiting mitogenic signaling and is mutated in Neurofibromatosis type II (NF2) disease, although its molecular mechanism is not fully understood. Here, we observed that Merlin inhibited Wnt/β-catenin signaling by blocking phosphorylation of LRP6, which is necessary for Wnt signal transduction, whereas mutated Merlin in NF2 patients did not. Treatment with Wnt3a enhanced phosphorylation of Ser518 in Merlin via activation of PAK1 in a PIP2-dependent manner. Phosphorylated Merlin dissociated from LRP6, allowing for phosphorylation of LRP6. Tissues from NF2 patients exhibited higher levels of β-catenin, and proliferation of RT4-D6P2T rat schwannoma cells was significantly reduced by treatment with chemical inhibitors of Wnt/β-catenin signaling. Taken together, our findings suggest that sustained activation of Wnt/β-catenin signaling due to abrogation of Merlin-mediated inhibition of LRP6 phosphorylation may be a cause of NF2 disease.
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