ArticleNature structural & molecular biology2016
Axin cancer mutants form nanoaggregates to rewire the Wnt signaling network.
Article in Nature structural & molecular biology, 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, 43 citations in OpenAlex.
- Hepatocellular carcinoma-linkediScience · 2026Article
- Characterization of BRCA1-Associated Protein-1 (BAP1) Aggregation Properties Induced by Cancer-Associated Mutations.Chembiochem : a European journal of chemical biology · 2025Article
- Canonical WNT/β-catenin signaling upregulates aerobic glycolysis in diverse cancer types.Molecular biology reports · 2024Review
- Analysis of Tumor-Associated AXIN1 Missense Mutations Identifies Variants That Activate β-Catenin Signaling.Cancer research · 2024Article
- AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia.American journal of human genetics · 2023Article
- Structural and Functional Insights into GID/CTLH E3 Ligase Complexes.International journal of molecular sciences · 2022Review
- Gαi2-induced conductin/axin2 condensates inhibit Wnt/β-catenin signaling and suppress cancer growth.Nature communications · 2022Article
- A comparison of four technologies for detecting p53 aggregates in ovarian cancer.Frontiers in oncology · 2022Article
- Wnt/β-catenin signaling in cancers and targeted therapies.Signal transduction and targeted therapy · 2021Review
- Osmolytes and crowders regulate aggregation of the cancer-related L106R mutant of the Axin protein.Biophysical journal · 2021Article
- Mutations and mechanisms of WNT pathway tumour suppressors in cancer.Nature reviews. Cancer · 2021Review
- Zooming in on the WNT/CTNNB1 Destruction Complex: Functional Mechanistic Details with Implications for Therapeutic Targeting.Handbook of experimental pharmacology · 2021Article
- Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association.Computational and structural biotechnology journal · 2021Article
- Targeting Casein Kinase 1 (CK1) in Hematological Cancers.International journal of molecular sciences · 2020Review
- RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer.The EMBO journal · 2020Article
- The Scaffold Protein Axin Promotes Signaling Specificity within the Wnt Pathway by Suppressing Competing Kinase Reactions.Cell systems · 2020Article
- Arginine π-stacking drives binding to fibrils of the Alzheimer protein Tau.Nature communications · 2020Article
- An aggregon in conductin/axin2 regulates Wnt/β-catenin signaling and holds potential for cancer therapy.Nature communications · 2019Article
- The mammalian CTLH complex is an E3 ubiquitin ligase that targets its subunit muskelin for degradation.Scientific reports · 2019Article
- Identification of Key Potential Targets and Pathway for Arsenic Trioxide by Systemic Bioinformatics Analysis in Pancreatic Cancer.Pathology oncology research : POR · 2019Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
Signaling cascades depend on scaffold proteins that regulate the assembly of multiprotein complexes. Missense mutations in scaffold proteins are frequent in human cancer, but their relevance and mode of action are poorly understood. Here we show that cancer point mutations in the scaffold protein Axin derail Wnt signaling and promote tumor growth in vivo through a gain-of-function mechanism. The effect is conserved for both the human and Drosophila proteins. Mutated Axin forms nonamyloid nanometer-scale aggregates decorated with disordered tentacles, which 'rewire' the Axin interactome. Importantly, the tumor-suppressor activity of both the human and Drosophila Axin cancer mutants is rescued by preventing aggregation of a single nonconserved segment. Our findings establish a new paradigm for misregulation of signaling in cancer and show that targeting aggregation-prone stretches in mutated scaffolds holds attractive potential for cancer treatment.
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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.