MPS1 kinase as a potential therapeutic target in medulloblastoma

Irina Alimova, June Ng, Peter Harris, Diane Birks, Andrew Donson, Michael D. Taylor, Nicholas K. Foreman, Sujatha Venkataraman, Rajeev Vibhakar

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2633-2640
Number of pages8
JournalOncology reports
Volume36
Issue number5
DOIs
StatePublished - Nov 2016
Externally publishedYes

Keywords

  • Kinase
  • MPS1
  • Medulloblastoma
  • Mitosis
  • NMS-P715

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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