Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma.

Scientific Reports
Sonia Simon SerranoMohamed Jemaà

Abstract

Neuroblastoma is the most common paediatric cancer type. Patients diagnosed with high-risk neuroblastoma have poor prognosis and occasionally tumours relapse. As a result, novel treatment strategies are needed for relapse and refractory neuroblastoma patients. Here, we found that high expression of Mps1 kinase (mitotic kinase Monopolar Spindle 1) was associated with relapse-free neuroblastoma patient outcomes and poor overall survival. Silencing and inhibition of Mps1 in neuroblastoma or PDX-derived cells promoted cell apoptosis via the caspase-dependent mitochondrial apoptotic pathway. The mechanism of cell death upon Mps1 inhibition was dependent on the polyploidization/aneuploidization of the cells before undergoing mitotic catastrophe. Furthermore, tumour growth retardation was confirmed in a xenograft mouse model after Mps1-inhibitor treatment. Altogether, these results suggest that Mps1 expression and inhibition can be considered as a novel prognostic marker as well as a therapeutic strategy for the treatment of high-risk neuroblastoma patients.

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Citations

Sep 12, 2021·Nature Reviews. Molecular Cell Biology·Helen K MatthewsRobertus A M de Bruin

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Methods Mentioned

BETA
flow cytometry
PCR
xenograft
flow-cytometry
transfection
FCS
FACS
Fluorescence

Software Mentioned

R2
Genomics
GraphPad
FCS Express

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis