Neuroblastoma Cells Depend on CSB for Faithful Execution of Cytokinesis and Survival.
Int J Mol Sci
; 22(18)2021 Sep 17.
Article
em En
| MEDLINE
| ID: mdl-34576232
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
DNA Helicases
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Interferência de RNA
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Enzimas Reparadoras do DNA
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Citocinese
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Proteínas de Ligação a Poli-ADP-Ribose
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Neuroblastoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article