ArticlePloS one2010
Cancer cells acquire mitotic drug resistance properties through beta I-tubulin mutations and alterations in the expression of beta-tubulin isotypes.
Article in PloS one, 2010. 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, 57 citations in OpenAlex.
- Ovarian Cancer Susceptibility and Chemosensitivity to KRAS Modulation.International journal of molecular sciences · 2026Article
- VERU-111, an orally available tubulin inhibitor, suppresses ovarian tumor growth and metastasis.The Journal of pharmacology and experimental therapeutics · 2025Article
- Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.Genes & diseases · 2024Review
- Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers.Acta pharmaceutica Sinica. B · 2023Review
- Ciliate Microtubule Diversities: Insights from the EFBTU3 Tubulin in the Antarctic CiliateMicroorganisms · 2022Article
- Tubulin-binding peptide RR-171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF-kappa B pathway.Cell proliferation · 2022Article
- Cytoskeletal Remodeling in Cancer.Biology · 2020Review
- Transcriptional responses in Parascaris univalens after in vitro exposure to ivermectin, pyrantel citrate and thiabendazole.Parasites & vectors · 2020Article
- Synthesis, Antiproliferative Activity and Molecular Docking Studies of Novel Doubly Modified Colchicine Amides and Sulfonamides as Anticancer Agents.Molecules (Basel, Switzerland) · 2020Article
- The Expression and Potential Role of Tubulin Alpha 1b in Wilms' Tumor.BioMed research international · 2020Article
- Review
- Resistance to anti-microtubule drug-induced cell death is determined by regulation of BimEL expression.Oncogene · 2019Article
- A Survey on Tubulin and Arginine Methyltransferase Families Sheds Light onInternational journal of molecular sciences · 2019Article
- In silico study of colchicine resistance molecular mechanisms caused by tubulin structural polymorphism.PloS one · 2019Article
- Immune-system-dependent anti-tumor activity of a plant-derived polyphenol rich fraction in a melanoma mouse model.Cell death & disease · 2016Article
- Tubulin Beta3 Serves as a Target of HDAC3 and Mediates Resistance to Microtubule-Targeting Drugs.Molecules and cells · 2015Article
- Synergistic cytotoxicity of cisplatin and Taxol in overcoming Taxol resistance through the inhibition of LDHA in oral squamous cell carcinoma.Oncology letters · 2015Article
- Schizophrenia and autism as contrasting minds: neural evidence for the hypo-hyper-intentionality hypothesis.Schizophrenia bulletin · 2015Article
- Article
- Apoptosis and molecular targeting therapy in cancer.BioMed research international · 2014Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnti-mitotic compounds (microtubule de-stabilizers) such as vincristine and vinblastine have been shown clinically successful in treating various cancers. However, development of drug-resistance cells limits their efficacies in clinical situations. Therefore, experiments were performed to determine possible drug resistance mechanisms related to the application of anti-mitotic cancer therapy. PRINCIPAL
findingsA KB-derived microtubule de-stabilizer-resistant KB-L30 cancer cell line was generated for this study. KB-L30 cells showed cross-resistance to various microtubule de-stabilizers including BPR0L075, vincristine and colchicine through multiple-drug resistant (MDR)-independent mechanisms. Surprisingly, KB-L30 cells showed hyper-sensitivity to the microtubule-stabilizer, paclitaxel. Results of the RT-PCR analysis revealed that expression of both class II and III β-tubulin was down-regulated in KB-L30 cells as compared to its parental KB cancer cells. In addition, DNA sequencing analysis revealed six novel mutation sites present in exon four of the βI-tubulin gene. Computational modeling indicated that a direct relationship exists between βI-tubulin mutations and alteration in the microtubule assembly and dynamic instability in KB-L30 cells and this predicted model was supported by an increased microtubule assembly and reduced microtubule dynamic instability in KB-L30 cells, as shown by Western blot analysis. CONCLUSIONS AND SIGNIFICANCE: Our study demonstrated that these novel mutations in exon four of the βI-tubulin induced resistance to microtubule de-stabilizers and hyper-sensitivity to microtubule stabilizer through an alteration in the microtubule assembly and dynamics in cancer cells. Importantly, the current study reveals that cancer cells may acquire drug resistance ability to anti-mitotic compounds through multiple changes in the microtubule networks. This study further provided molecular information in drug selection for patients with specific tubulin mutations.
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