ArticleBreast cancer research : BCR2019
WDR5 inhibition halts metastasis dissemination by repressing the mesenchymal phenotype of breast cancer cells.
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Lactate-induced H3K4me3 histone mark promotes PLOD1-driven prostate cancer invasion.Cell death & disease · 2026Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- A histone-centric multi-omics study shows that increased H3K4 methylation sustains triple-negative breast cancer phenotypes.Nature communications · 2025Article
- Epigenetic regulation of cancer stemness.Signal transduction and targeted therapy · 2025Review
- The Wdr5-H3K4me3 Epigenetic Axis Regulates Pancreatic Tumor Immunogenicity and Immune Suppression.International journal of molecular sciences · 2024Article
- The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancer.Cell death and differentiation · 2024Article
- WD Repeat Domain 5 Inhibitors for Cancer Therapy: Not What You Think.Journal of clinical medicine · 2024Review
- Article
- PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities.Molecules (Basel, Switzerland) · 2023Review
- Structure-based discovery of potent WD repeat domain 5 inhibitors that demonstrate efficacy and safety in preclinical animal models.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- RhoC in association with TET2/WDR5 regulates cancer stem cells by epigenetically modifying the expression of pluripotency genes.Cellular and molecular life sciences : CMLS · 2022Article
- Human WDR5 promotes breast cancer growth and metastasis via KMT2-independent translation regulation.eLife · 2022Article
- WIN site inhibition disrupts a subset of WDR5 function.Scientific reports · 2022Article
- Histone modification and histone modification-targeted anti-cancer drugs in breast cancer: Fundamentals and beyond.Frontiers in pharmacology · 2022Review
- DDX21 Interacts with WDR5 to Promote Colorectal Cancer Cell Proliferation by Activating CDK1 Expression.Journal of Cancer · 2022Article
- The roles of epigenetics in cancer progression and metastasis.The Biochemical journal · 2021Review
- The subtype-specific molecular function of SPDEF in breast cancer and insights into prognostic significance.Journal of cellular and molecular medicine · 2021Article
- Cancer drug resistance induced by EMT: novel therapeutic strategies.Archives of toxicology · 2021Review
- WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1α accumulation in Myc-dependent and independent pathways.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Structural insights into the recognition of histone H3Q5 serotonylation by WDR5.Science advances · 2021Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDevelopment of metastases and drug resistance are still a challenge for a successful systemic treatment in breast cancer (BC) patients. One of the mechanisms that confer metastatic properties to the cell relies in the epithelial-to-mesenchymal transition (EMT). Moreover, both EMT and metastasis are partly modulated through epigenetic mechanisms, by repression or induction of specific related genes.
methodsWe applied shRNAs and drug targeting approaches in BC cell lines and metastatic patient-derived xenograft (PDX) models to inhibit WDR5, the core subunit of histone H3 K4 methyltransferase complexes, and evaluate its role in metastasis regulation.
resultWe report that WDR5 is crucial in regulating tumorigenesis and metastasis spreading during BC progression. In particular, WDR5 loss reduces the metastatic properties of the cells by reverting the mesenchymal phenotype of triple negative- and luminal B-derived cells, thus inducing an epithelial trait. We also suggest that this regulation is mediated by TGFβ1, implying a prominent role of WDR5 in driving EMT through TGFβ1 activation. Moreover, such EMT reversion can be induced by drug targeting of WDR5 as well, leading to BC cell sensitization to chemotherapy and enhancement of paclitaxel-dependent effects.
conclusionsWe suggest that WDR5 inhibition could be a promising pharmacologic approach to reduce cell migration, revert EMT, and block metastasis formation in BC, thus overcoming resistance to standard treatments.
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