ArticleNature chemical biology2025
Cholesterol-targeting Wnt-β-catenin signaling inhibitors for colorectal cancer.
Article in Nature chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed.
- PI(3,5)PScience advances · 2026Article
- Colorectal Cancer: Epidemiology, Risk Factors, Signaling Pathways, Clinical Features, Screening, Diagnosis, and Management.MedComm · 2026Review
- STRAP promotes hepatocellular carcinoma progression through activation of an STRAP/Wnt-β-catenin/STRAP positive feedback loop.iScience · 2026Article
- CircSPARC promotes esophageal squamous cell carcinoma through an HNRNPC-EPN2 splicing axis that activates Wnt/β-Catenin signaling.Molecular cancer · 2026Article
- Loss of Mast cells and histaminergic signaling link diet to platelet-mediated NETosis and mammary cancer recurrence.bioRxiv : the preprint server for biology · 2026Article
- Boosting immunotherapy by restoring cryptic APC function.Cell research · 2026Article
- Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells.Science advances · 2026Article
- Testicular microcystic stromal tumor: a case report with MRI findings and literature review.American journal of translational research · 2026Article
- Research Advances in Nanodrugs Targeting Lipid Metabolism Reprogramming for Colorectal Cancer Therapy.International journal of nanomedicine · 2026Review
- Targeting PTPN13 with 11-amino-acid peptides of C-terminal APC prevents immune evasion of colorectal cancer.Cell research · 2026Article
- SP1-IKBIP axis promotes the proliferation and invasion of glioma with Wnt/β-catenin associated epithelial-mesenchymal transition.American journal of cancer research · 2026Article
- Neutrophils exposed to a cholesterol metabolite secrete extracellular vesicles that promote epithelial-mesenchymal transition and stemness in breast cancer cells.Cancer letters · 2026Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Disruption of cholesterol homeostasis by antidepressants induces immunogenic cell death.Oncoimmunology · 2025Article
- Trimming the fat from Dishevelled.Nature chemical biology · 2025Article
- Multidisciplinary collaborative enhanced recovery after surgery nursing in patients with colorectal cancer: A comparative study.World journal of gastrointestinal oncology · 2025Article
- The paradigm shift: re-evaluating preclinical animal models for colorectal cancer in the precision medicine era.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Most persons with colorectal cancer (CRC) carry adenomatous polyposis coli (APC) truncation leading to aberrant Wnt-β-catenin signaling; however, effective targeted therapy for them is lacking as the mechanism by which APC truncation drives CRC remains elusive. Here, we report that the cholesterol level in the inner leaflet of the plasma membrane (IPM) is elevated in all tested APC-truncated CRC cells, driving Wnt-independent formation of Wnt signalosomes through Dishevelled (Dvl)-cholesterol interaction. Cholesterol-Dvl interaction inhibitors potently blocked β-catenin signaling in APC-truncated CRC cells and suppressed their viability. Because of low IPM cholesterol level and low Dvl expression and dependence, normal cells including primary colon epithelial cells were not sensitive to these inhibitors. In vivo testing with a xenograft mouse model showed that our inhibitors effectively suppressed truncated APC-driven tumors without causing intestinal toxicity. Collectively, these results suggest that the most common type of CRC could be effectively and safely treated by blocking the cholesterol-Dvl-β-catenin signaling axis.
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Registered trials
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