ArticleNature communications2019
Anti-LRP5/6 VHHs promote differentiation of Wnt-hypersensitive intestinal stem cells.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- E3 ubiquitin-ligase Hakai regulates LRP4 stability and Wnt/β-catenin signalling in colorectal cancer cells.iScience · 2026Article
- A dual-pathway Wnt-IL-13 fusion protein enhances human intestinal regeneration through tuft cell activation.The Journal of biological chemistry · 2026Article
- Activation of SLIT2/ROBO1/LRP6 axis aggravates cartilage degradation via β-catenin signaling in TMJOA.JCI insight · 2026Article
- A Small-Molecule SLD1121 Activates Wnt/β-Catenin Signaling and Promotes Hair Growth via Targeting the Wnt Coreceptor LRP6.JACS Au · 2026Article
- Manipulation of Wnt/β-Catenin Signaling by Synthetic Frizzled Agonist and LRP Antagonist in Organoid Cultures and In Vivo.Small methods · 2026Article
- Article
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- The emerging role of intestinal stem cells in ulcerative colitis.Frontiers in medicine · 2025Review
- E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled receptors.Life science alliance · 2024Article
- Deciphering the spatiotemporal transcriptional landscape of intestinal diseases (Review).Molecular medicine reports · 2024Review
- Multifaceted effects of LRP6 in cancer: exploring tumor development, immune modulation and targeted therapies.Medical oncology (Northwood, London, England) · 2024Review
- Evolutionary and functional analyses of LRP5 in archaic and extant modern humans.Human genomics · 2024Article
- 14-3-3ε: a protein with complex physiology function but promising therapeutic potential in cancer.Cell communication and signaling : CCS · 2024Review
- Quartz Crystal Microbalance Platform for SARS-CoV-2 Immuno-Diagnostics.International journal of molecular sciences · 2023Article
- A TRIM21-based bioPROTAC highlights the therapeutic benefit of HuR degradation.Nature communications · 2023Article
- The strategies to cure cancer patients by eradicating cancer stem-like cells.Molecular cancer · 2023Review
- Regulation of cell proliferation and transdifferentiation compensates for ventilator-induced lung injury mediated by NLRP3 inflammasome activation.Immunity, inflammation and disease · 2023Review
- Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for coreceptor discrimination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Relationship between LRP6 and Wnt/β-Catenin Pathway in Colorectal and Esophageal Cancer.Life (Basel, Switzerland) · 2023Article
- Blocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure.Nature communications · 2022Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wnt-induced β-catenin-mediated transcription is a driving force for stem cell self-renewal during adult tissue homeostasis. Enhanced Wnt receptor expression due to mutational inactivation of the ubiquitin ligases RNF43/ZNRF3 recently emerged as a leading cause for cancer development. Consequently, targeting canonical Wnt receptors such as LRP5/6 holds great promise for treatment of such cancer subsets. Here, we employ CIS display technology to identify single-domain antibody fragments (VHH) that bind the LRP6 P3E3P4E4 region with nanomolar affinity and strongly inhibit Wnt3/3a-induced β-catenin-mediated transcription in cells, while leaving Wnt1 responses unaffected. Structural analysis reveal that individual VHHs variably employ divergent antigen-binding regions to bind a similar surface in the third β-propeller of LRP5/6, sterically interfering with Wnt3/3a binding. Importantly, anti-LRP5/6 VHHs block the growth of Wnt-hypersensitive Rnf43/Znrf3-mutant intestinal organoids through stem cell exhaustion and collective terminal differentiation. Thus, VHH-mediated targeting of LRP5/6 provides a promising differentiation-inducing strategy for treatment of Wnt-hypersensitive tumors.
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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.