ArticleScientific reports2021
HDAC6 inhibitors sensitize non-mesenchymal triple-negative breast cancer cells to cysteine deprivation.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Current and future therapies for triple-negative breast cancer.Journal of hematology & oncology · 2026Review
- Selenium-Thioredoxin Axis Contributes to Ferroptosis Resistance in Pancreatic Cancer Cells.International journal of molecular sciences · 2026Article
- FSP1 and histone deacetylases suppress cancer persister cell ferroptosis.Science advances · 2026Article
- Recent Insights into the Creation of Histone Deacetylase Inhibitors for the Treatment of Human Diseases.International journal of molecular sciences · 2025Review
- Regulation of HDAC6 Catalytic Activity in Cancer: The Role of Post-Translational Modifications and Protein-Protein Interactions.International journal of molecular sciences · 2025Review
- Lysine deacetylase inhibitors have low selectivity in cells and exhibit predominantly off-target effects.FEBS open bio · 2025Article
- Article
- Cystine/cysteine metabolism regulates the progression and response to treatment of triple‑negative breast cancer (Review).Oncology letters · 2024Review
- Programming a Ferroptosis-to-Apoptosis Transition Landscape Revealed Ferroptosis Biomarkers and Repressors for Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Chitosan-loaded piperlongumine nanoparticles and kaempferol enhance the anti-cancer action of doxorubicin in targeting of Ehrlich solid adenocarcinoma: in vivo and in silico modeling study.Medical oncology (Northwood, London, England) · 2024Article
- Genetic Variants at PRKCG Splice and UTR Sites Promote Cancer Susceptibility by Disrupting Epigenetic and miRNA Regulatory Network.Journal of Cancer · 2024Article
- Article
- Adverse Crosstalk between Extracellular Matrix Remodeling and Ferroptosis in Basal Breast Cancer.Cells · 2023Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Identification of Novel Natural Dual HDAC and Hsp90 Inhibitors for Metastatic TNBC Using e-Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Studies.Molecules (Basel, Switzerland) · 2023Article
- Potential Therapies Targeting the Metabolic Reprogramming of Diabetes-Associated Breast Cancer.Journal of personalized medicine · 2023Review
- Development of doxorubicin hydrochloride-loaded whey protein nanoparticles and its surface modification with N-acetyl cysteine for triple-negative breast cancer.Drug delivery and translational research · 2022Article
- First-in-Class Dual Mechanism Ferroptosis-HDAC Inhibitor Hybrids.Journal of medicinal chemistry · 2022Article
- Review
- Two Sides of the Same Coin: Protein Kinase C γ in Cancer and Neurodegeneration.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) is a highly malignant type of breast cancer and lacks effective therapy. Targeting cysteine-dependence is an emerging strategy to treat the mesenchymal TNBC. However, many TNBC cells are non-mesenchymal and unresponsive to cysteine deprivation. To overcome such resistance, three selective HDAC6 inhibitors (Tubacin, CAY10603, and Tubastatin A), identified by epigenetic compound library screening, can synergize with cysteine deprivation to induce cell death in the non-mesenchymal TNBC. Despite the efficacy of HDAC6 inhibitor, knockout of HDAC6 did not mimic the synthetic lethality induced by its inhibitors, indicating that HDAC6 is not the actual target of HDAC6 inhibitor in this context. Instead, transcriptomic profiling showed that tubacin triggers an extensive gene transcriptional program in combination with erastin, a cysteine transport blocker. Notably, the zinc-related gene response along with an increase of labile zinc was induced in cells by the combination treatment. The disturbance of zinc homeostasis was driven by PKCγ activation, which revealed that the PKCγ signaling pathway is required for HDAC6 inhibitor-mediated synthetic lethality. Overall, our study identifies a novel function of HDAC6 inhibitors that function as potent sensitizers of cysteine deprivation and are capable of abolishing cysteine-independence in non-mesenchymal TNBC.
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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.