Targeting the Chromosomal Passenger Complex Subunit INCENP Induces Polyploidization, Apoptosis, and Senescence in Neuroblastoma.

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