ArticleProceedings of the National Academy of Sciences of the United States of America2015
Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 157 citations in OpenAlex.
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
- Precision Medicine in Pancreatic Cancer: Targeting KRAS and Beyond.Targeted oncology · 2026Review
- Research on Targeted Therapy for Malignant Tumors of the Biliary Tract.OncoTargets and therapy · 2026Review
- Epithelial WNT secretion drives niche escape of developing gastric cancer.Molecular cancer · 2025Article
- BRAFiScience · 2025Article
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Spanish consensus on the diagnosis and management of adrenocortical carcinoma.Endocrine-related cancer · 2025Review
- Targeting PAR-2-driven inflammatory pathways in colorectal cancer: mechanistic insights from atorvastatin and rosuvastatin treatment in cell line models.Translational cancer research · 2025Article
- Comprehensive genomic dependency landscape of a human colon cancer organoid.Communications biology · 2025Article
- Drug Treatment Direction Based on the Molecular Mechanism of Breast Cancer Brain Metastasis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- LGR5: An emerging therapeutic target for cancer metastasis and chemotherapy resistance.Cancer metastasis reviews · 2025Review
- Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?Pharmaceuticals (Basel, Switzerland) · 2024Review
- New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- Navigating through novelties concerning mCRC treatment-the role of immunotherapy, chemotherapy, and targeted therapy in mCRC.Frontiers in surgery · 2024Review
- New insights into the unfolded protein response (UPR)-anterior gradient 2 (AGR2) pathway in the regulation of intestinal barrier function in weaned piglets.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Review
- Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2.Science advances · 2023Article
- The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options.Cells · 2023Review
- The Roles of Secreted Wnt Ligands in Cancer.International journal of molecular sciences · 2023Review
- The tumor biological significance of RNF43 and LRP1B in gastric cancer is complex and context-dependent.Scientific reports · 2023Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
44 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Rnf43 (RING finger protein 43) and Znrf3 (zinc/RING finger protein 3) (RZ) are two closely related transmembrane E3 ligases, encoded by Wnt target genes, that remove surface Wnt (wingless-int) receptors. The two genes are mutated in various human cancers. Such tumors are predicted to be hypersensitive to, yet still depend on, secreted Wnts. We previously showed that mutation of RZ in the intestine yields rapidly growing adenomas containing LGR5(+) (leucine-rich repeat-containing G-protein coupled receptor 5) stem cells and Wnt3-producing Paneth cells. We now show that removal of Paneth cells by Math1 mutation inhibits RZ(-/-) tumor formation. Similarly, deletion of Wnt3 inhibits tumorigenesis. Treatment of mice carrying RZ(-/-) intestinal neoplasia with a small molecule Wnt secretion inhibitor (porcupine inhibitor C59) strongly inhibited growth, whereas adjacent normal crypts remained intact. These results establish that paracrine Wnt secretion is an essential driver of RZ(-/-) tumor growth and imply that a therapeutic window exists for the use of porcupine inhibitors for RZ-mutant 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.