ArticleInternational journal of oncology2020
Dexamethasone inhibits stemness maintenance and enhances chemosensitivity of hepatocellular carcinoma stem cells by inducing deSUMOylation of HIF‑1α and Oct4.
Article in International journal of oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Effect of hepatic arterial dexamethasone administration on long-term survival among hepatocellular carcinoma patients undergoing transcatheter arterial chemoembolization.BMC anesthesiology · 2026Article
- Targeting SUMOylation in glioblastoma: A novel avenue for therapy and biomarker discovery.Genes & diseases · 2026Review
- SUMOylation Inhibitor TAK-981 Alleviates Hallmark Features of Preeclampsia Related to High Glucocorticoid Exposure by Inhibiting Placental Oxidative Stress in Rats.Antioxidants (Basel, Switzerland) · 2026Article
- Glucocorticoids induce femoral head necrosis in rats through the HIF-1α/VEGF signaling pathway.Scientific reports · 2025Article
- Mitochondrial transplantation sensitizes chemotherapy to inhibit tumor development by enhancing anti-tumor immunity.Cancer biology & medicine · 2025Article
- Comprehensive SUMO Proteomic Analyses Identify HIV Latency-Associated Proteins in Microglia.Cells · 2025Article
- Integrative analysis of multi-omics data identified PLG as key gene related to Anoikis resistance and immune phenotypes in hepatocellular carcinoma.Journal of translational medicine · 2024Article
- The SUMO Family: Mechanisms and Implications in Thyroid Cancer Pathogenesis and Therapy.Biomedicines · 2024Review
- Dexamethasone-tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells.Bioscience reports · 2024Article
- Abnormal protein SUMOylation in liver disease: novel target for therapy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems.Stem cell reviews and reports · 2022Review
- Dexamethasone promotes breast cancer stem cells in obese and not lean mice.Pharmacology research & perspectives · 2022Article
- Mild Hypothermia Promotes Ischemic Tolerance and Survival of Neural Stem Cell Grafts by Enhancing Global SUMOylation.Oxidative medicine and cellular longevity · 2022Article
- Protein sumoylation in normal and cancer stem cells.Frontiers in molecular biosciences · 2022Review
- The Role of Protein SUMOylation in Human Hepatocellular Carcinoma: A Potential Target of New Drug Discovery and Development.Cancers · 2021Review
- SENP2 Reduces Hepatocellular Carcinoma Stemness and Improves Sorafenib Sensitivity Through Inactivating the AKT/GSK3β/CTNNB1 Pathway.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been controversial whether patients with hepatocellular carcinoma (HCC) should receive glucocorticoid therapy during chemotherapy. Recent studies have demonstrated that glucocorticoids increase the therapeutic sensitivity of tumors to some chemotherapeutic drugs, but the specific mechanism remains unclear. In the present study, dexamethasone (Dex) was used to treat HCC stem cells. The results demonstrated that Dex reduced stemness maintenance and self‑renewal of HCC stem cells, promoted epithelial‑to‑mesenchymal transition, inhibited migration and angiogenesis and, more importantly, increased cell sensitivity to the herpes simplex virus thymidine kinase/ganciclovir drug system in vitro and in vivo. Further mechanistic analyses demonstrated that Dex inhibited small ubiquitin‑like modifier (SUMO) modification of several proteins in HCC stem cells, including hypoxia‑inducible factor (HIF)‑1α, an important hypoxia tolerance protein, and octamer‑binding transcription factor 4 (Oct4), a crucial stemness maintenance protein. Inducing deSUMOylation of HIF‑1α and Oct4 reduced their accumulation in the nucleus, thereby inhibiting tumor angiogenesis and stemness maintenance. These findings provide a new perspective to the study of the mechanism underlying the anti‑hepatocarcinogenesis effects of Dex. Due to the few side effects of glucocorticoids at low doses and their anti‑inflammatory effects, the appropriate combination of glucocorticoids and chemotherapeutic drugs is expected to improve the survival of HCC patients and their prognosis.
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