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MPS1 kinase as a potential therapeutic target in medulloblastoma.
- Source :
-
Oncology reports [Oncol Rep] 2016 Nov; Vol. 36 (5), pp. 2633-2640. Date of Electronic Publication: 2016 Sep 12. - Publication Year :
- 2016
-
Abstract
- Medulloblastoma is the most common type of malignant brain tumor that affects children. Although recent advances in chemotherapy and radiation have improved outcomes, high-risk patients perform poorly with significant morbidity. Gene expression profiling has revealed that monopolar spindle 1 (MPS1) (TTK1) is highly expressed in medulloblastoma patient samples compared to that noted in normal cerebellum. MPS1 is a key regulator of the spindle assembly checkpoint (SAC), a mitotic mechanism specifically required for proper chromosomal alignment and segregation. The SAC can be activated in aneuploid cancer cells and MPS1 is overexpressed in many types of cancers. A previous study has demonstrated the effectiveness of inhibiting MPS1 with small-molecule inhibitors, but the role of MPS1 in medulloblastoma is unknown. In the present study, we demonstrated that MPS1 inhibition by shRNA or with a small-molecule drug, NMS-P715, resulted in decreased cell growth, inhibition of clonogenic potential and induction of apoptosis in cells belonging to both the Shh and group 3 medulloblastoma genomic signature. These findings highlight MPS1 as a rational therapeutic target for medulloblastoma.
- Subjects :
- Cell Cycle drug effects
Cell Cycle Proteins antagonists & inhibitors
Cell Cycle Proteins genetics
Cell Proliferation drug effects
Gene Expression Regulation, Neoplastic drug effects
HeLa Cells
Humans
M Phase Cell Cycle Checkpoints drug effects
Medulloblastoma drug therapy
Medulloblastoma pathology
Mitosis genetics
Protein Serine-Threonine Kinases antagonists & inhibitors
Protein Serine-Threonine Kinases genetics
Protein-Tyrosine Kinases antagonists & inhibitors
Protein-Tyrosine Kinases genetics
Pyrazoles administration & dosage
Quinazolines administration & dosage
Apoptosis drug effects
Cell Cycle Proteins biosynthesis
Medulloblastoma genetics
Molecular Targeted Therapy
Protein Serine-Threonine Kinases biosynthesis
Protein-Tyrosine Kinases biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 27633003
- Full Text :
- https://doi.org/10.3892/or.2016.5085