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Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma

Simon Serrano, Sonia LU ; Sime, Wondossen LU ; Abassi, Yasmin LU ; Daams, Renée LU ; Massoumi, Ramin LU and Jemaà, Mohamed LU (2020) In Scientific Reports 10(1). p.11997-11997
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... (More)

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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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
pages
11997 - 11997
publisher
Nature Publishing Group
external identifiers
  • pmid:32686724
  • scopus:85088259209
ISSN
2045-2322
DOI
10.1038/s41598-020-68829-y
language
English
LU publication?
yes
additional info
These authors jointly supervised this work: Ramin Massoumi and Mohamed Jemaà.
id
0a5bf038-535f-45c3-a936-c0568e45c778
date added to LUP
2020-07-22 12:43:21
date last changed
2025-10-18 02:27:34
@article{0a5bf038-535f-45c3-a936-c0568e45c778,
  abstract     = {{<p>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.</p>}},
  author       = {{Simon Serrano, Sonia and Sime, Wondossen and Abassi, Yasmin and Daams, Renée and Massoumi, Ramin and Jemaà, Mohamed}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{1}},
  pages        = {{11997--11997}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-68829-y}},
  doi          = {{10.1038/s41598-020-68829-y}},
  volume       = {{10}},
  year         = {{2020}},
}