Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma

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Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma. / Simon Serrano, Sonia; Sime, Wondossen; Abassi, Yasmin; Daams, Renée; Massoumi, Ramin; Jemaà, Mohamed.

I: Scientific Reports, Vol. 10, Nr. 1, 20.07.2020, s. 11997.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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T1 - Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma

AU - Simon Serrano, Sonia

AU - Sime, Wondossen

AU - Abassi, Yasmin

AU - Daams, Renée

AU - Massoumi, Ramin

AU - Jemaà, Mohamed

N1 - These authors jointly supervised this work: Ramin Massoumi and Mohamed Jemaà.

PY - 2020/7/20

Y1 - 2020/7/20

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-020-68829-y

DO - 10.1038/s41598-020-68829-y

M3 - Article

C2 - 32686724

VL - 10

SP - 11997

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -