Inhibition of Mitotic Kinase Mps1 Promotes Cell Death in Neuroblastoma

Overview

Journal Sci Rep

Specialty Science

Date 2020 Jul 21

PMID 32686724

Citations 10

Authors

Sonia Simon Serrano

Wondossen Sime

Yasmin Abassi

Renee Daams

Ramin Massoumi

Mohamed Jemaa

Affiliations

Soon will be listed here.

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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