ArticleCancers2020
Inhibition of Wnt/β-Catenin Signaling in Neuroendocrine Tumors in vitro: Antitumoral Effects.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Genomic and Transcriptomic Landscapes of MEN1-Wild-Type Low-Grade Metastatic Pancreatic NETs Uncover Key Oncogenic Drivers and Targetable Pathways.International journal of biological sciences · 2026Article
- Telotristat ethyl affects tumour-fibroblast crosstalk in small intestinal neuroendocrine tumours.Journal of neuroendocrinology · 2025Article
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- Potential of C-X-C-Chemokine-Receptor-Type-4-Directed PET/CT Using [¹⁸F]AlF-NOTA-QHY-04 in Identifying Molecular Subtypes of Small Cell Lung Cancer.Korean journal of radiology · 2025Article
- Genetic insight into lung neuroendocrine tumors: Notch and Wnt signaling pathways as potential targets.Journal of translational medicine · 2025Article
- Article
- Review
- The Management of Phaeochromocytomas and Paragangliomas in the Era of Precision Medicine: Where Are We Now? Evidence-Based Systemic Treatment Options and Future Cluster Oriented Perspectives.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Everything you ever wanted to know about cancer stem cells in neuroendocrine neoplasms but were afraid to ask.Endocrine oncology (Bristol, England) · 2024Review
- Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments.Theranostics · 2024Review
- Management of pheochromocytomas and paragangliomas: Review of current diagnosis and treatment options.Cancer medicine · 2023Review
- Combinations of PRI-724 Wnt/β-Catenin Pathway Inhibitor with Vismodegib, Erlotinib, or HS-173 Synergistically Inhibit Head and Neck Squamous Cancer Cells.International journal of molecular sciences · 2023Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review).International journal of oncology · 2023Review
- Novel preclinical gastroenteropancreatic neuroendocrine neoplasia models demonstrate the feasibility of mutation-based targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Genomic characterization reveals distinct mutation landscapes and therapeutic implications in neuroendocrine carcinomas of the gastrointestinal tract.Cancer communications (London, England) · 2022Article
- Targeted Therapies in Pheochromocytoma and Paraganglioma.The Journal of clinical endocrinology and metabolism · 2022Review
- Targeted Therapy for Adrenocortical Carcinoma: A Genomic-Based Search for Available and Emerging Options.Cancers · 2022Article
- Personalized Management of Pheochromocytoma and Paraganglioma.Endocrine reviews · 2022Review
- Multiomic Analysis of Lung Tumors Defines Pathways Activated in Neuroendocrine Transformation.Cancer discovery · 2021Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsInhibition of Wnt/β-catenin signaling by specific inhibitors is currently being investigated as an antitumoral strategy for various cancers. The role of Wnt/β-catenin signaling in neuroendocrine tumors still needs to be further investigated.
methodsThis study investigated the antitumor activity of the porcupine (PORCN) inhibitor WNT974 and the β-catenin inhibitor PRI-724 in human neuroendocrine tumor (NET) cell lines BON1, QGP-1, and NCI-H727 in vitro. NET cells were treated with WNT974, PRI-724, or small interfering ribonucleic acids against β-catenin, and subsequent analyses included cell viability assays, flow cytometric cell cycle analysis, caspase3/7 assays and Western blot analysis.
resultsTreatment of NET cells with WNT974 significantly reduced NET cell viability in a dose- and time-dependent manner by inducing NET cell cycle arrest at the G1 and G2/M phases without inducing apoptosis. WNT974 primarily blocked Wnt/β-catenin signaling by the dose- and time-dependent downregulation of low-density lipoprotein receptor-related protein 6 (LRP6) phosphorylation and non-phosphorylated β-catenin and total β-catenin, as well as the genes targeting the latter (c-Myc and cyclinD1). Furthermore, the WNT974-induced reduction of NET cell viability occurred through the inhibition of GSK-3-dependent or independent signaling (including pAKT/mTOR, pEGFR and pIGFR signaling). Similarly, treatment of NET cells with the β-catenin inhibitor PRI-724 caused significant growth inhibition, while the knockdown of β-catenin expression by siRNA reduced NET tumor cell viability of BON1 cells but not of NCI-H727 cells.
conclusionsThe PORCN inhibitor WNT974 possesses antitumor properties in NET cell lines by inhibiting Wnt and related signaling. In addition, the β-catenin inhibitor PRI-724 possesses antitumor properties in NET cell lines. Future studies are needed to determine the role of Wnt/β-catenin signaling in NET as a potential therapeutic target.
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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.