ArticleLaboratory investigation; a journal of technical methods and pathology2016
Targeting the Wnt/β-catenin pathway in primary ovarian cancer with the porcupine inhibitor WNT974.
Article in Laboratory investigation; a journal of technical methods and pathology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 70 citations in OpenAlex.
- Palmitoylated importin α recruits PKCε to the plasma membrane to drive breast cancer cell motility.bioRxiv : the preprint server for biology · 2026Article
- Clinical and Functional Characterization of PDE1A as a Wnt/Oncology research · 2026Article
- WNT signaling in cancer: molecular mechanisms and potential therapies.Molecular biomedicine · 2025Review
- Identification of a TNIK-CDK9 Axis as a Targetable Strategy for Platinum-Resistant Ovarian Cancer.Molecular cancer therapeutics · 2025Article
- RSPO3 induced by Helicobacter pylori extracts promotes gastric cancer stem cell properties through the GNG7/β-catenin signaling pathway.Cancer medicine · 2024Article
- RSPO2 as Wnt signaling enabler: Important roles in cancer development and therapeutic opportunities.Genes & diseases · 2024Review
- Long non-coding RNA NRSN2-AS1 promotes ovarian cancer progression through targeting PTK2/β-catenin pathway.Cell death & disease · 2023Article
- Review
- 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
- "DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies.Frontiers in oncology · 2023Review
- Signaling pathways and their potential therapeutic utility in esophageal squamous cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Metabolic Alterations and WNT Signaling Impact Immune Response in HGSOC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Combination of artesunate and WNT974 induces KRAS protein degradation by upregulating E3 ligase ANACP2 and β-TrCP in the ubiquitin-proteasome pathway.Cell communication and signaling : CCS · 2022Article
- Icariin attenuates the tumor growth by targeting miR-1-3p/TNKS2/Wnt/β-catenin signaling axis in ovarian cancer.Frontiers in oncology · 2022Article
- Review
- Determination of the membrane topology of PORCN, an O-acyl transferase that modifies Wnt signalling proteins.Open biology · 2021Article
- Targeting Wnt Signaling in Endometrial Cancer.Cancers · 2021Review
- Targeting of Deregulated Wnt/β-Catenin Signaling by PRI-724 and LGK974 Inhibitors in Germ Cell Tumor Cell Lines.International journal of molecular sciences · 2021Article
- LGK974 suppresses lipopolysaccharide-induced endotoxemia in mice by modulating the crosstalk between the Wnt/β-catenin and NF-κB pathways.Experimental & molecular medicine · 2021Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Preclinical studies in ovarian cancer have demonstrated upregulation of the Wnt/β-catenin pathway promoting tumor proliferation and chemoresistance. Our objective was to evaluate the effect of the Wnt/β-catenin pathway inhibitor, WNT974, in primary ovarian cancer ascites cells. Ascites cells from patients with papillary serous ovarian cancer were isolated and treated with 1 μM WNT974±100 μM carboplatin. Viability was evaluated with the ATPlite assay. The IC50 was calculated using a dose-response analysis. Immunohistochemistry (IHC) was performed on ascites cells and tumor. Expression of R-spondin 2 (RSPO2), RSPO3, PORCN, WLS, AXIN2, and three previously characterized RSPO fusion transcripts were assessed using Taqman assays. Sixty ascites samples were analyzed for response to WNT974. The ascites samples that showed a decrease in ATP concentration after treatment demonstrated no difference from the untreated cells in percent viability with trypan blue staining. Flow cytometry demonstrated fewer cells in the G2 phase and more in the G1 and S phases after treatment with WNT974. Combination therapy with WNT974 and carboplatin resulted in a higher percentage of samples that showed ≥30% reduction in ATP concentration than either single drug treatment. IHC analysis of Wnt pathway proteins suggests cell cycle arrest rather than cytotoxicity after WNT974 treatment. QPCR indicated that RSPO fusions are not prevalent in ovarian cancer tissues or ascites. However, higher PORCN expression correlated to sensitivity to WNT974 (P=0.0073). In conclusion, WNT974 produces cytostatic effects in patient ascites cells with primary ovarian cancer through inhibition of the Wnt/β-catenin pathway. The combination of WNT974 and carboplatin induces cytotoxicity plus cell cycle arrest in a higher percentage of ascites samples than with single drug treatment. RSPO fusions do not contribute to WNT974 sensitivity; however, higher PORCN expression indicates increased WNT974 sensitivity.
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