Targeting the chromosomal passenger complex subunit INCENP induces polyploidization, apoptosis, and senescence in neuroblastoma

Veronica Veschi, Veronica Veschi, Zhihui Liu, Ming Sun, Man Xu, Sukriti Bagchi, Man Xu, Carol J. Thiele, Arnulfo Mendoza

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)4937-4950
Number of pages14
JournalCancer Research
Volume79
Publication statusPublished - 2019

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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