Chromosomal passenger complex (CPC) has been demma cell lines in vitro and decreased the growth of neuroonstrated to be a potential target of cancer therapy by blastoma xenografts in vivo, with significant increases inhibiting Aurora B or survivin in different types of cancer in murine survival. Mechanistically, INCENP depletion sup-including neuroblastoma. However, chemical inhibition pressed neuroblastoma cell growth by inducing polyploidiof either Aurora B or survivin does not target CPC specifzation, apoptosis, and senescence. In most neuroblastoma ically due to off-target effects or CPC-independent activities cell lines tested in vitro, apoptosis was the primary cell of these two components. In a previous chromatin-focused fate after INCENP silencing due to induction of DNA dam-siRNA screen, we found that neuroblastoma cells were age response and activation of the p53–p21 axis. These particularly vulnerable to loss of INCENP, a gene encoding results confirm that CPC is a therapeutic target in neuroa key scaffolding component of the CPC. In this study, blastoma, and targeting INCENP is a novel way to disrupt INCENP was highly expressed by neuroblastoma cells, the activity of CPC and inhibit tumor progression in neu- and its expression decreased following retinoic acid–roblastoma. induced neuroblastoma differentiation. Elevated levels of INCENP were significantly associated with poor prognosis in Significance: Dysregulation of INCENP contributes to primary tumors of neuroblastoma patients with high-risk neuroblastoma tumorigenesis and targeting INCENP predisease. Genetic silencing of INCENP reduced the growth of sents a novel strategy to disrupt the activity of chromosomal both MYCN–wild-type and MYCN-amplified neuroblastopassenger complex and inhibit neuroblastoma progression.
|Numero di pagine||14|
|Stato di pubblicazione||Published - 2019|
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