ArticleOncogene2017
Phosphorylation of cofilin-1 by ERK confers HDAC inhibitor resistance in hepatocellular carcinoma cells via decreased ROS-mediated mitochondria injury.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Ameliorative impact of sacubitril/valsartan on paraquat-induced acute lung injury: role of Nrf2 and TLR4/NF-κB signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Erk1/2 Orchestrates SSPH I-Induced Oxidative Stress, Mitochondrial Dysfunction and Ferroptosis in Hepatocellular Carcinoma.Journal of cellular and molecular medicine · 2025Article
- Disrupting CARMA3 Signaling with Triptolide Reverses Sorafenib Resistance in Hepatocellular Carcinoma.International journal of medical sciences · 2025Article
- Cytoskeleton Remodeling-Related Proteins Represent a Specific Salivary Signature in PSC Patients.Molecules (Basel, Switzerland) · 2024Article
- Sensitization of hepatocellular carcinoma cells to HDACi is regulated through hsa-miR-342-5p/CFL1.Cancer cell international · 2024Article
- Cytoskeletal and Cytoskeleton-Associated Proteins: Key Regulators of Cancer Stem Cell Properties.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review
- Article
- Oxaloacetate acid ameliorates paraquat-induced acute lung injury by alleviating oxidative stress and mitochondrial dysfunction.Frontiers in pharmacology · 2022Article
- Combining histone deacetylase inhibitors (HDACis) with other therapies for cancer therapy.European journal of medicinal chemistry · 2021Review
- Overexpressed Proteins in HCC Cell-Derived Exosomes, CCT8, and Cofilin-1 Are Potential Biomarkers for Patients with HCC.Diagnostics (Basel, Switzerland) · 2021Article
- Hsa-miR-107 regulates chemosensitivity and inhibits tumor growth in hepatocellular carcinoma cells.Aging · 2021Article
- Hypoxia-induced cofilin 1 promotes hepatocellular carcinoma progression by regulating the PLD1/AKT pathway.Clinical and translational medicine · 2021Article
- Cyclovirobuxine D Induces Apoptosis and Mitochondrial Damage in Glioblastoma Cells Through ROS-Mediated Mitochondrial Translocation of Cofilin.Frontiers in oncology · 2021Article
- Role of cofilin‑1 in arsenic trioxide‑induced apoptosis of NB4‑R1 cells.Molecular medicine reports · 2020Article
- Hydrogen Sulfide Attenuates Hydrogen Peroxide-Induced Injury in Human Lung Epithelial A549 Cells.International journal of molecular sciences · 2019Article
- Article
- Combination treatment strategy for pancreatic cancer involving the novel HDAC inhibitor MPT0E028 with a MEK inhibitor beyond K-Ras status.Clinical epigenetics · 2019Article
- Oxaloacetate Ameliorates Chemical Liver Injury via Oxidative Stress Reduction and Enhancement of Bioenergetic Fluxes.International journal of molecular sciences · 2018Article
- Cofilin-2 Acts as a Marker for Predicting Radiotherapy Response and Is a Potential Therapeutic Target in Nasopharyngeal Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Despite the availability of several treatment strategies, resistance to chemotherapeutic agents, which limits the effectiveness of anticancer drugs, is a major problem in cancer therapy. In this study, we used a histone deacetylases inhibitor (HDACi) to establish drug-resistant HCC cells and further analyzed the molecular mechanisms underlying the development of resistance in HCC cells. Compared with the parental cells, HDACi-resistant cells showed high metastatic and pro-survival abilities. Two-dimensional electrophoresis data showed that the cofilin-1 (CFL-1) protein was altered in HDACi-resistant cells and was highly expressed in resistant cells compared with parental cells. The molecular function of CFL-1 is actin depolymerization, and it is involved in tumor metastasis. In this study, we showed that CFL-1 inhibition decreased cell migration and increased cell apoptosis in HDACi-resistant cells. We observed that HDACi induced ROS accumulation in cells and apoptosis via promotion of the CFL-1 interaction with Bax and CFL-1 translocation to the mitochondria, resulting in cytochrome C release. Importantly, phosphorylation of CFL-1 by activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) confers strong protection against HDAC inhibitor-induced cell injury. p-CFL-1 shows a loss of affinity with Bax and will not translocate to mitochondria, stably remaining in the cytoplasm. These results indicate that phosphorylation to inactivate CFL-1 decreased the chemosensitivity to HDAC inhibitors and resulting in drug resistance of HCC cells.
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