ArticleSignal transduction and targeted therapy2023
Histone deacetylase inhibitors promote breast cancer metastasis by elevating NEDD9 expression.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- DNA methylation in monozygotic twins discordant for acute lymphoblastic leukemia: a case report and systematic review.Clinical epigenetics · 2025Pooled it
- Hydroxamic Acids as HDAC Inhibitor Drug Leads for Malaria.Medicinal research reviews · 2026Review
- Elp3 activates the JNK/MAPK pathway through histone acetylation to promote gastric cancer proliferation, migration, and invasion.Histology and histopathology · 2026Article
- Single-stranded DNA in the bone microenvironment promotes prostate cancer bone metastasis via the ITGA6-FAK pathway.Communications biology · 2026Article
- Steroidogenic Acute Regulatory Protein in Breast Cancer: Mechanistic Insights into Pathogenesis and Therapeutics.International journal of molecular sciences · 2026Review
- Epigenetic regulation in cancer metastasis.Discover oncology · 2026Review
- Harnessing Substituted 4-Chlorothieno[2,3-Pharmaceuticals (Basel, Switzerland) · 2026Article
- Clinical progress and functional modalities of HDAC inhibitor-based combination therapies in cancer treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Functional and Mechanistic Insights of 3-Hydroxybutyrate (3-OBA) in Bladder Cancer.Molecules (Basel, Switzerland) · 2025Article
- Design and synthesis of polymer nanoparticles with pH-responsive pan-HDAC inhibitor (C5) derived from norbornene block copolymers to increase C5 solubility and improve its targeted delivery to prostate cancer sites.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Emerging Nanozyme Strategies for Precision Breast Cancer Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Lactylation-mediated miRNA regulation in cancer therapy resistance.Journal of translational medicine · 2025Review
- EIF4A3 Promotes Muscle Atrophy and Aging by Inhibiting the FAK Pathway Through NEDD9 mRNA Destabilization.Journal of cachexia, sarcopenia and muscle · 2025Article
- Histone hyperacetylation disrupts spermatogonial stem cells homeostasis and impairs spermiogenesis.Stem cell research & therapy · 2025Article
- Effects of SB939 are mediated by STAT3 to inhibit breast cancer cell metastasis-related genes.Oncology letters · 2025Article
- Polymer model integrates imaging and sequencing to reveal how nanoscale heterochromatin domains influence gene expression.Nature communications · 2025Article
- Review
- Nuclear to Cytoplasmic Transport Is a Druggable Dependency in HDAC7-driven Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Histone acetylation modulators in breast cancer.Breast cancer research : BCR · 2025Review
- Decoding the Epigenome of Breast Cancer.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase (HDAC) is a kind of protease that modifies histone to regulate gene expression, and is usually abnormally activated in tumors. The approved pan-HDAC inhibitors have demonstrated clinical benefits for patients in some hematologic malignancies. Only limited therapeutic success in breast cancer has been observed in clinical trials. In this study, we declare that pan-HDAC inhibitors targeting NEDD9-FAK pathway exacerbate breast cancer metastasis in preclinical models, which may severely impede their clinical success. NEDD9 is not an oncogene, however, it has been demonstrated recently that there are high level or activity changes of NEDD9 in a variety of cancer, including leukemia, colon cancer, and breast cancer. Mechanistically, pan-HDAC inhibitors enhance H3K9 acetylation at the nedd9 gene promoter via inhibition of HDAC4 activity, thus increase NEDD9 expression, and then activate FAK phosphorylation. The realization that pan-HDAC inhibitors can alter the natural history of breast cancer by increasing invasion warrants clinical attention. In addition, although NEDD9 has been reported to have a hand in breast cancer metastasis, it has not received much attention, and no therapeutic strategies have been developed. Notably, we demonstrate that FAK inhibitors can reverse breast cancer metastasis induced by upregulation of NEDD9 via pan-HDAC inhibitors, which may offer a potential combination therapy for breast cancer.
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