ArticleJournal of experimental & clinical cancer research : CR2024
HDAC1/2 control mesothelium/ovarian cancer adhesive interactions impacting on Talin-1-α5β1-integrin-mediated actin cytoskeleton and extracellular matrix protein remodeling.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Chromatin remodelling: a driving force in reverse mechanotransduction.RNA biology · 2026Review
- Gastric cancer-secreted galectin-1 promotes peritoneal mesothelial-mesenchymal transition to prime peritoneal metastasis soil.iScience · 2026Article
- Disruption of thrombospondin 1/2-integrin β1 axis impairs cell adhesion and tumor growth in intrahepatic cholangiocarcinoma.Cell death discovery · 2026Article
- Development of Biphenyl-Substituted Uracil-Based Hydroxamic Acids (UBHAs) as Potent HDAC Inhibitors with Pro-Apoptotic Activity in Leukemia and Prostate Cancer Cells.Journal of medicinal chemistry · 2026Article
- Platinum-resistant ovarian cancer: From mechanisms to treatment strategies.Genes & diseases · 2026Review
- Integrative network toxicology and molecular docking reveal epigenetic and endocrine-disrupting mechanisms of PFAS in ovarian cancer.Frontiers in pharmacology · 2026Article
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Anti-metastatic potential of flavonoids for the treatment of cancers: focus on epithelial-mesenchymal transition (EMT) process.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- PRRSV promotes bacterial infection by remodeling actin cytoskeleton and cell membrane proteins.mBio · 2025Article
- Long noncoding RNA H19 promotes the acquisition of a mesenchymal-like invasive phenotype in mesothelial primary cells through an HDAC1-mediated WT1/Sp1 switch.Cell death & disease · 2025Article
- RAD23B Promotes Colorectal Cancer Metastasis via the Talin1/Integrin/PI3K/AKT/MMP9 Axis.Oncology research · 2025Article
- Targeted inhibition of integrin αVβ3 induces cytotoxicity and suppresses migration ability in ovarian cancer cells and tumor spheroids.International journal of medical sciences · 2025Article
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Authors and funding
20 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPeritoneal metastasis, which accounts for 85% of all epithelial ovarian carcinoma (EOC) metastases, is a multistep process that requires the establishment of adhesive interactions between cancer cells and the peritoneal membrane. Interrelations between EOC and the mesothelial stroma are critical to facilitate the metastatic process. No data is available so far on the impact of histone acetylation/deacetylation, a potentially relevant mechanism governing EOC metastasis, on mesothelial cells (MCs)-mediated adhesion.
methodsStatic adhesion and peritoneal clearance experiments were performed pretreating mesenchymal-like MCs and platinum-sensitive/resistant EOC cell lines with MS-275-a Histone deacetylase (HDAC)1-3 pharmacological inhibitor currently used in combination trials. Results were acquired by confocal microscopy and were analyzed with an automated Opera software. The role of HDAC1/2 was validated by genetic silencing. The role of α4-, α5-α1 Integrins and Fibronectin-1 was validated using specific monoclonal antibodies. Quantitative proteomic analysis was performed on primary MCs pretreated with MS-275. Decellularized matrices were generated from either MS-275-exposed or untreated cells to study Fibronectin-1 extracellular secretion. The effect of MS-275 on β1 integrin activity was assessed using specific monoclonal antibodies. The role of Talin-1 in MCs/EOC adhesion was analyzed by genetic silencing. Talin-1 ectopic expression was validated as a rescue tool from MS-275-induced phenotype. The in vivo effect of MS-275-induced MC remodeling was validated in a mouse model of peritoneal EOC dissemination.
resultsTreatment of MCs with non-cytotoxic concentrations of MS-275 caused a consistent reduction of EOC adhesion. Proteomic analysis revealed several pathways altered upon MC treatment with MS-275, including ECM deposition/remodeling, adhesion receptors and actin cytoskeleton regulators. HDAC1/2 inhibition hampered actin cytoskeleton polymerization by downregulating actin regulators including Talin-1, impairing β1 integrin activation, and leading to abnormal extracellular secretion and distribution of Fibronectin-1. Talin-1 ectopic expression rescued EOC adhesion to MS-275-treated MCs. In an experimental mouse model of metastatic EOC, MS-275 limited tumor invasion, Fibronectin-1 secretion and the sub-mesothelial accumulation of MC-derived carcinoma-associated fibroblasts.
conclusionOur study unveils a direct impact of HDAC-1/2 in the regulation of MC/EOC adhesion and highlights the regulation of MC plasticity by epigenetic inhibition as a potential target for therapeutic intervention in EOC peritoneal metastasis.
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