MPS1 kinase as a potential therapeutic target in medulloblastoma
| Autor: | Irina Alimova, Rajeev Vibhakar, Andrew M. Donson, Nicholas K. Foreman, June Ng, Peter Harris, Sujatha Venkataraman, Michael D. Taylor, Diane K. Birks |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Pathology medicine.medical_specialty NMS-P715 kinase Apoptosis Cell Cycle Proteins Biology Protein Serine-Threonine Kinases medulloblastoma 03 medical and health sciences 0302 clinical medicine medicine Humans Molecular Targeted Therapy Clonogenic assay MPS1 Mitosis Cell Proliferation Medulloblastoma mitosis Oncogene Cell Cycle Cancer General Medicine Articles Cell cycle Protein-Tyrosine Kinases medicine.disease 3. Good health Gene Expression Regulation Neoplastic Spindle checkpoint 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research Quinazolines M Phase Cell Cycle Checkpoints Pyrazoles HeLa Cells |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 1021-335X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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