Neuroblastoma Cells Depend on CSB for Faithful Execution of Cytokinesis and Survival
Autor: | Silvia Filippi, Elena Paccosi, Alessio Balzerano, Stefano Brancorsini, Michele Costantino, Luca Proietti-De-Santis |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
DNA Repair
Cell division Cell Apoptosis Cockayne syndrome Cell Movement Biology (General) Poly-ADP-Ribose Binding Proteins Spectroscopy Caspase Tumor biology Caspase 3 General Medicine gene therapy Caspase 9 Computer Science Applications Chemistry medicine.anatomical_structure cell death RNA Interference Cell Survival DNA repair QH301-705.5 Context (language use) Spindle Apparatus Article Catalysis Cell Line Inorganic Chemistry neuroblastoma Cell Line Tumor Neuroblastoma medicine Humans Physical and Theoretical Chemistry Cockayne Syndrome Molecular Biology QD1-999 Cell Proliferation Cytokinesis Centrosome cytokinesis failure Organic Chemistry DNA Helicases medicine.disease DNA Repair Enzymes biology.protein Cancer research |
Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 10070, p 10070 (2021) International Journal of Molecular Sciences Volume 22 Issue 18 |
ISSN: | 1661-6596 1422-0067 |
Popis: | Neuroblastoma, the most common extra-cranial solid tumor of early childhood, is one of the major therapeutic challenges in child oncology: it is highly heterogenic at a genetic, biological, and clinical level. The high-risk cases have one of the least favorable outcomes amongst pediatric tumors, and the mortality rate is still high, regardless of the use of intensive multimodality therapies. Here, we observed that neuroblastoma cells display an increased expression of Cockayne Syndrome group B (CSB), a pleiotropic protein involved in multiple functions such as DNA repair, transcription, mitochondrial homeostasis, and cell division, and were recently found to confer cell robustness when they are up-regulated. In this study, we demonstrated that RNAi-mediated suppression of CSB drastically impairs tumorigenicity of neuroblastoma cells by hampering their proliferative, clonogenic, and invasive capabilities. In particular, we observed that CSB ablation induces cytokinesis failure, leading to caspases 9 and 3 activation and, subsequently, to massive apoptotic cell death. Worthy of note, a new frontier in cancer treatment, already proved to be successful, is cytokinesis-failure-induced cell death. In this context, CSB ablation seems to be a new and promising anticancer strategy for neuroblastoma therapy. |
Databáze: | OpenAIRE |
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