ArticleStem cell research & therapy2021
EIF5A2 enhances stemness of epithelial ovarian cancer cells via a E2F1/KLF4 axis.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Targeting eIF5A2 hypusination with bikinin sensitizes hepatocellular carcinoma to lenvatinib by suppressing TFEB-mediated autophagy.Human cell · 2026Article
- E2F1-autophagy-ALDH1A1 axis enhances self-renewal and drug resistance of lung cancer stem-like cells in a p53-dependent manner.Journal of experimental & clinical cancer research : CR · 2025Article
- E2F1 Facilitates the Proliferation and Stemness of Gastric Cancer Cells by Activating CDC25B Transcription and Modulating the MAPK Pathway.Biochemical genetics · 2025Article
- Manipulation of Oxygen Tension in Damaged Regions via Hypoxia-Induced IPN Hydrogel Microspheres for Intervertebral Disc Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Knocking down RAD51AP1 enhances chemosensitivity by inhibiting the self-renewal of CD133 positive ovarian cancer stem-like cells.Discover oncology · 2024Article
- Article
- Bioinspired Bone Seed 3D-Printed Scaffold via Trapping Black Phosphorus Nanosheet for Bone Regeneration.Small science · 2024Article
- Long non-coding RNA RAD51-AS1 promotes the tumorigenesis of ovarian cancer by elevating EIF5A2 expression.Journal of cancer research and clinical oncology · 2024Article
- Targeting eIF5A2 reduces invasion and reverses chemoresistance in SCC-9 cellsHistology and histopathology · 2024Article
- Research progress of epithelial-mesenchymal transformation-related transcription factors in peritoneal metastases.Journal of Cancer · 2024Review
- Black Phosphorus Accelerates Bone Regeneration Based on Immunoregulation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Genetic and Functional Modifications Associated with Ovarian Cancer Cell Aggregation and Limited Culture Conditions.International journal of molecular sciences · 2023Article
- Review
- Article
- High TRB3 expression induces chondrocyte autophagy and senescence in osteoarthritis cartilage.Aging · 2022Article
- Initiation and elongation factor co-expression correlates with recurrence and survival in epithelial ovarian cancer.Journal of ovarian research · 2022Article
- The osteoprotective role of USP26 in coordinating bone formation and resorption.Cell death and differentiation · 2022Article
- Emerging Role of E2F Family in Cancer Stem Cells.Frontiers in oncology · 2021Review
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
backgroundOvarian cancer stem cells (OCSC), endowed with tumor-initiating and self-renewal capacity, would account not only for the tumor growth, the peritoneal metastasis, and the relapse, but also for the acquisition of chemotherapy resistance. Nevertheless, figuring out their phenotypical and functional traits has proven quite challenging, mainly because of the heterogeneity of ovarian cancer. A deeper understanding of OCSC mechanisms will shed light on the development of the disease. Therefore, we aim to explore it for the design of innovative treatment regimens which aim at the eradication of ovarian cancer through the elimination of the CSC component.
methodsIn this study, immunohistochemistry assay and western blot assay were used to detect protein expression in the primary tumor and peritoneal multi-cellular aggregates/spheroids (MCAs/MCSs). OCSCs induced from cell line SKOV3 and HO-8910 were enriched in a serum-free medium (SFM). The effect of EIF5A2 on CSC-like properties was detected by sphere-forming assays, re-differentiation assays, quantitative real-time polymerase chain reaction, western blotting, flow cytometry, cell viability assays, immunofluorescence staining, and in vivo xenograft experiments. RNA-sequencing (RNA-seq) was used to reveal the mechanism by which EIF5A2 positively modulates the stem-like properties of ovarian cancer cells.
resultsExpression of EIF5A2 was significantly higher in peritoneal MCAs/MCSs compared to matched primary tumors, and EIF5A2 was also unregulated in ovarian cancer cell line-derived spheroids. Knockdown of EIF5A2 reduced the expression of the stem-related markers (ALDH1A1 and OCT-4), inhibited self-renewal ability, improved the sensitivity to chemotherapeutic drugs, and inhibited tumorigenesis in vivo. Mechanistic studies revealed that EIF5A2 knockdown reduced the expression of KLF4, which could partially rescue stem-like properties abolished by EIF5A2 knockdown or strengthened by EIF5A2 overexpression, through the transcription factor E2F1, which directly bind to KLF4 promoter.
conclusionOur results imply that EIF5A2 positively regulates stemness in ovarian cancer cells via E2F1/KLF4 pathway and may serve as a potential target in CSCs-targeted therapy for ovarian cancer.
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