ArticleInternational journal of oncology2018
S-phase kinase-associated protein 2 is involved in epithelial-mesenchymal transition in methotrexate-resistant osteosarcoma cells.
Article in International journal of oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Understanding and Overcoming Osteosarcoma Heterogeneity.Biomolecules · 2026Review
- An injectable thermosensitive PLGA-PEG-PLGA hydrogel integrated with coordination-driven self-assembled MTX-Mn nanoparticles for enhanced melanoma therapyRSC advances · 2026Article
- Combating Methotrexate Resistance in Cancer Treatment: A Review on Navigating Pathways and Enhancing Its Efficacy With Fat-Soluble Vitamins.Scientifica · 2025Review
- LncRNA HOXA-AS3 promotes cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma.Scientific reports · 2024Article
- Single-cell RNA sequencing reveals the communications between tumor microenvironment components and tumor metastasis in osteosarcoma.Frontiers in immunology · 2024Article
- Regulation of the Epithelial to Mesenchymal Transition in Osteosarcoma.Biomolecules · 2023Review
- Targeting the untargetable: RB1-deficient tumours are vulnerable to Skp2 ubiquitin ligase inhibition.British journal of cancer · 2022Review
- Characterization of Vemurafenib-Resistant Melanoma Cell Lines Reveals Novel Hallmarks of Targeted Therapy Resistance.International journal of molecular sciences · 2022Article
- Article
- LncRNA SCAMP1 disrupts the balance between miR-26a-5p and ZEB2 to promote osteosarcoma cell viability and invasion.Frontiers in oncology · 2022Article
- Phytochemical library screening reveals betulinic acid as a novel Skp2-SCF E3 ligase inhibitor in non-small cell lung cancer.Cancer science · 2021Article
- Overview of Evidence-Based Chemotherapy for Oral Cancer: Focus on Drug Resistance Related to the Epithelial-Mesenchymal Transition.Biomolecules · 2021Review
- Review
- MiR-506 exerts antineoplastic effects on osteosarcoma cells via inhibition of the Skp2 oncoprotein.Aging · 2021Article
- Identification of key biomarkers and functional pathways in osteosarcomas with lung metastasis: Evidence from bioinformatics analysis.Medicine · 2021Article
- Review
- Review
- Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies.International journal of molecular sciences · 2020Review
- Skp2 modulates proliferation, senescence and tumorigenesis of glioma.Cancer cell international · 2020Article
- F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.Theranostics · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma (OS), a common worldwide primary aggressive bone malignancy, arises from primitive transformed cells of mesenchymal origin and usually attacks adolescents and young adults. Methotrexate (MTX) is the anti-folate drug used as a pivotal chemotherapeutic agent in the treatment of OS. However, patients with OS often develop drug resistance, leading to poor treatment outcomes. In the present study, in order to explore the underlying mechanisms responsible for MTX resistance, we established MTX‑resistant OS cells using the U2OS and MG63 cell lines and examined whether MTX‑resistant OS cells underwent epithelial-mesenchymal transition (EMT) by Transwell assay, wound healing assay, MTT assay, RT-PCR and western blot analysis. We found that the viability of the MTX‑resistant cells remained relatively unaltered following further treatment with MTX compared to the parental cells. The resistant cells appeared to possess a mesenchymal phenotype, with an elongated and more spindle‑like shape, and acquired enhanced invasive, migratory and attachment abilities. The measurement of EMT markers also supported EMT transition in the MTX‑resistant OS cells. Our result further demonstrated that the overexpression of S-phase kinase-associated protein 2 (Skp2) was closely involved in the resistance of OS cells to MTX and in the acquirement of EMT properties. Thus, the pharmacological inhibition of Skp2 may prove to be a novel therapeutic strategy with which to overcome drug resistance in OS.
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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.