ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2022
Aberrant Cholesterol Metabolism and Wnt/β-Catenin Signaling Coalesce via Frizzled5 in Supporting Cancer Growth.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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The trial behind it
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Who cites it
64 citing papers in PubMed, 72 citations in OpenAlex.
- A synergistic cascade nanoreactor breaks bladder cancer chemoresistance: Synergizing cholesterol metabolism reprogramming with cGAS-STING-mediated metallotherapy.Materials today. Bio · 2026Article
- Cholesterol metabolism dysregulation in eyelid sebaceous gland carcinoma and its clinical significance.Indian journal of ophthalmology · 2026Article
- ZDHHC18-Mediated Palmitoylation of ORF3a Promotes SARS-CoV-2 Pathogenesis by Antagonizing TRIM16-Mediated Ubiquitination and Proteasomal Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Expression, prognostic value and function of LMBR1L in gastric cancer.Molecular genetics and genomics : MGG · 2026Article
- Targeting tumor-associated G-protein coupled receptors: beyond single-axis inhibition toward multidimensional regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Pancreatic cancer EMT‑targeted therapy: Molecular mechanisms and clinical translation (Review).International journal of oncology · 2026Review
- Wnt signaling promotes inflammation and EMT-associated gene expression in mesenchymal TNBC.Scientific reports · 2026Article
- Cancer Cell-Intrinsic Cholesterol Induces Lipid-Associated Macrophage Differentiation via SP1 Palmitoylation to Promote Prostate Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cholesterol Metabolism-related Characteristics Predict Therapeutic Response and Survival in Esophageal Cancer.Journal of advanced research · 2026Article
- Lipid metabolism in pancreatic cancer treatment.World journal of clinical oncology · 2026Review
- Role of Oxysterol-Binding Protein Family in Cholesterol Metabolism and Cancer Progression: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- ZDHHC-Mediated Protein S-Palmitoylation in Cancer: Epigenetic Interfaces, Structural Logic and Therapeutic Targeting.International journal of medical sciences · 2026Review
- The SOX10-ACAT2-Cholesterol Synthesis Axis Is Required for Melanoma Proliferation.International journal of biological sciences · 2026Article
- SYTL5 drives malignant progression in differentiated thyroid carcinoma: unveiling its regulatory mechanisms.Frontiers in oncology · 2026Article
- The Roles of ProteinCancer communications (London, England) · 2026Review
- Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review).International journal of molecular medicine · 2025Review
- Cholesterol metabolism on stem cell fate determination: a frontier horizon.Stem cell research & therapy · 2025Review
- Lipid metabolism and lipid signaling in extracellular vesicles ontogeny: from biogenesis to functional execution.Journal of nanobiotechnology · 2025Review
- Wnt induces FZD5/8 endocytosis and degradation and the involvement of RSPO-ZNRF3/RNF43 and DVL.eLife · 2025Article
- RPL6 Interacts with HMGCS1 to Stabilize HIF-1α by Promoting Cholesterol Production in Hepatocellular Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
Abstract
Frizzled (Fzd) proteins are Wnt receptors and play essential roles in development, homeostasis, and oncogenesis. How Wnt/Fzd signaling is coupled to physiological regulation remains unknown. Cholesterol is reported as a signaling molecule regulating morphogen such as Hedgehog signaling. Despite the elusiveness of the in-depth mechanism, it is well-established that pancreatic cancer specially requires abnormal cholesterol metabolism levels for growth. In this study, it is unexpectedly found that among ten Fzds, Fzd5 has a unique capacity to bind cholesterol specifically through its conserved extracellular linker region. Cholesterol-binding enables Fzd5 palmitoylation, which is indispensable for receptor maturation and trafficking to the plasma membrane. In Wnt-addicted pancreatic ductal adenocarcinoma (PDAC), cholesterol stimulates tumor growth via Fzd5-mediated Wnt/β-catenin signaling. A natural oxysterol, 25-hydroxylsterol competes with cholesterol and inhibits Fzd5 maturation and Wnt signaling, thereby alleviating PDAC growth. This cholesterol-receptor interaction and ensuing receptor lipidation uncover a novel mechanism by which Fzd5 acts as a cholesterol sensor and pivotal connection coupling lipid metabolism to morphogen signaling. These findings further suggest that cholesterol-targeting may provide new therapeutic opportunities for treating Wnt-dependent cancers.
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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.