Neuroblastoma Cells Depend on CSB for Faithful Execution of Cytokinesis and Survival

International Journal of Molecular Sciences

卷:22

Luca Proietti-De-Santis¹  Michele Costantino¹  Silvia Filippi¹  Elena Paccosi¹  Alessio Balzerano¹  Stefano Brancorsini² 

[1] Unit of Molecular Genetics of Aging, Department of Ecology and Biology, University of Tuscia, 01100 Viterbo, Italy;

[2] Unit of Molecular Pathology, Department of Experimental Medicine, Section of Terni, University of Perugia, 06100 Perugia, Italy;

关键词: neuroblastoma;    cytokinesis failure;    cell death;    gene therapy;    Cockayne Syndrome;   

DOI  :  10.3390/ijms221810070

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown