ArticleEMBO molecular medicine2021
WNT inhibition creates a BRCA-like state in Wnt-addicted cancer.
Article in EMBO molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 65 citations in OpenAlex.
- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- Unravelling TPX2-centered co-expression networks as key drivers of aggressive prostate cancer.Scientific reports · 2025Article
- Targeting FZD6 creates therapeutically actionable vulnerabilities for advanced prostate cancer.Oncogene · 2025Article
- Alteration of Hyaluronic Acid Metabolism in Tumor Microenvironment Can Modulate DNA Repair Gene Expression: Therapeutic Potential for Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Article
- Lnc5q21.2, a novel long intergenic RNA, sensitizes colorectal cancer cells to ATR inhibitor by activating Wnt pathway.Journal of translational internal medicine · 2025Article
- Wnt/β-catenin mediated signaling pathways in cancer: recent advances, and applications in cancer therapy.Molecular cancer · 2025Review
- Review
- The paradigm shift: re-evaluating preclinical animal models for colorectal cancer in the precision medicine era.Frontiers in immunology · 2025Review
- Targeted therapy for liver cancer: Current status and future directions.BioImpacts : BI · 2025Review
- PARylation-mediated post-transcriptional modifications in cancer immunity and immunotherapy.Frontiers in immunology · 2025Review
- JPI-547, a Dual Inhibitor of PARP/Tankyrase, Shows Antitumor Activity Against Pancreatic Cancers with Homologous Recombination Repair Deficiency or Wnt-Addiction.International journal of biological sciences · 2025Article
- Epigenetic silencingCancer biology & therapy · 2024Article
- Nuclear porcupine mediates XRCC6/Ku70 S-palmitoylation in the DNA damage response.Experimental hematology & oncology · 2024Article
- Elucidating the genotoxicity of Fusobacterium nucleatum-secreted mutagens in colorectal cancer carcinogenesis.Gut pathogens · 2024Article
- Ultra-large scale virtual screening identifies a small molecule inhibitor of the Wnt transporter Wntless.iScience · 2024Article
- Single-nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands.Clinical and translational medicine · 2024Article
- PARP1-stabilised FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway.Oncogene · 2024Article
- The cholesterol biosynthesis enzyme FAXDC2 couples Wnt/β-catenin to RTK/MAPK signaling.The Journal of clinical investigation · 2024Article
- Hallmarks of stemness in mammalian tissues.Cell stem cell · 2024Review
- ELISL: early-late integrated synthetic lethality prediction in cancer.Bioinformatics (Oxford, England) · 2024Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Wnt signaling maintains diverse adult stem cell compartments and is implicated in chemotherapy resistance in cancer. PORCN inhibitors that block Wnt secretion have proven effective in Wnt-addicted preclinical cancer models and are in clinical trials. In a survey for potential combination therapies, we found that Wnt inhibition synergizes with the PARP inhibitor olaparib in Wnt-addicted cancers. Mechanistically, we find that multiple genes in the homologous recombination and Fanconi anemia repair pathways, including BRCA1, FANCD2, and RAD51, are dependent on Wnt/β-catenin signaling in Wnt-high cancers, and treatment with a PORCN inhibitor creates a BRCA-like state. This coherent regulation of DNA repair genes occurs in part via a Wnt/β-catenin/MYBL2 axis. Importantly, this pathway also functions in intestinal crypts, where high expression of BRCA and Fanconi anemia genes is seen in intestinal stem cells, with further upregulation in Wnt-high APC
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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.