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.

Targeting the chromosomal passenger complex subunit INCENP induces polyploidization, apoptosis, and senescence in neuroblastoma / Sun, M.; Veschi, V.; Bagchi, S.; Xu, M.; Mendoza, A.; Liu, Z.; Thiele, C. J.. - In: CANCER RESEARCH. - ISSN 0008-5472. - 79:19(2019), pp. 4937-4950. [10.1158/0008-5472.CAN-19-0695]

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

Veschi V.;
2019

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.
2019
INCENP/CPC/Polyploidy/DNA damage/Apoptosis/Senescence
01 Pubblicazione su rivista::01a Articolo in rivista
Targeting the chromosomal passenger complex subunit INCENP induces polyploidization, apoptosis, and senescence in neuroblastoma / Sun, M.; Veschi, V.; Bagchi, S.; Xu, M.; Mendoza, A.; Liu, Z.; Thiele, C. J.. - In: CANCER RESEARCH. - ISSN 0008-5472. - 79:19(2019), pp. 4937-4950. [10.1158/0008-5472.CAN-19-0695]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1698867
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