ArticleThe Journal of biological chemistry2018
Oligomerization of Frizzled and LRP5/6 protein initiates intracellular signaling for the canonical WNT/β-catenin pathway.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Liver fibrosis: Pathogenesis and innovative nanoparticle-based therapeutic strategies.International journal of pharmaceutics: X · 2026Review
- Wnt/β-Catenin Pathway and Hydraulic Calcium Silicate-Based Cements: A Narrative Review.Dentistry journal · 2026Review
- Targeting β-catenin: PROTACs and precision degraders for Wnt-driven cancers.Frontiers in oncology · 2026Review
- Progress on novel compounds for the treatment of bone metabolism-related disorders: focus on osteoporosis and beyond.Frontiers in chemistry · 2026Review
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Discoidin, CUB and LCCL domain containing 2 modulates angiogenesis by inhibiting VEGF receptor 2 endocytosis in endothelial cells.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Transcriptomic Analysis ofAnimals : an open access journal from MDPI · 2025Article
- frizzled 5 mutant zebrafish are genetically sensitised to developing microphthalmia and coloboma.Disease models & mechanisms · 2025Article
- Multi-omics integrated analysis reveals the molecular mechanism of tail fat deposition differences in sheep with different tail types.BMC genomics · 2025Article
- Variational Approaches for Drug-Disease-Gene Links in Periodontal Inflammation.International dental journal · 2025Article
- Frizzled receptors: gatekeepers of Wnt signaling in development and disease.Frontiers in cell and developmental biology · 2025Review
- Homozygosity for a hypomorphic mutation in frizzled class receptor 5 causes syndromic ocular coloboma with microcornea in humans.Human genetics · 2024Article
- Inhibiting histone deacetylase 6 suppresses the proliferation of microvascular endothelial cells by epigenetically activating miR-375-3p, potentially contributing to bone loss during mechanical unloading.Journal of translational medicine · 2024Article
- Structural insights into Frizzled3 through nanobody modulators.Nature communications · 2024Article
- Review
- Mechanistic Insights and Therapeutic Strategies in Osteoporosis: A Comprehensive Review.Biomedicines · 2024Review
- Exploring Heparan Sulfate Proteoglycans as Mediators of Human Mesenchymal Stem Cell Neurogenesis.Cellular and molecular neurobiology · 2024Review
- Review
- Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers.Microorganisms · 2023Review
- A genetic variant of the Wnt receptor LRP6 accelerates synapse degeneration during aging and in Alzheimer's disease.Science advances · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon binding to the canonical WNT glycoproteins, Frizzled family receptors (FZDs) and low-density lipoprotein receptor-related protein 5/6 (LRP5/6) undergo a series of polymerizations on the cell surface that elicit canonical WNT/β-catenin signaling. The hyperactivation of WNT/β-catenin signaling is the major cause of tumorigenesis, but the mechanism in tumors such as hepatoma remains unclear. Here, we observed that WNT3A manifested the hyperactivity in β-catenin-dependent signaling after binding to FZD's competitive inhibitory molecule secreted Frizzled-related protein 2 (SFRP2). To understand the mechanism of FZDs in the presence of SFRP2, we explored how FZDs can bind and activate the LRP5/6 signalosome independently of WNT glycoproteins. Our findings further revealed that oligomerizations of FZDs and LRP5/6 can integrate the cytoplasmic protein Dishevelled into the LRP5/6 signalosome, resulting in a robust activation of ligand-independent β-catenin signaling. We propose that besides WNT-bridged FZD-WNT-LRP5/6 protein complexes, the homo- and hetero-oligomerizations of WNT receptors may contribute to the formation of the LRP5/6 signalosome on the cell surface. Of note, we identified four highly expressed FZDs in the hepatoma cell line HepG2, all of which significantly promoted ligand-independent LRP5/β-catenin signaling. As FZDs are ectopically expressed in numerous tumors, our findings may provide a new perspective on tumor pathologies. Furthermore, the results in our study suggest that the composition and stoichiometry of FZDs and LRP5/6 within the LRP5/6 signalosome may tune the selection of bound WNT glycoproteins and configure downstream WNT/β-catenin signaling.
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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.