ArticleBritish journal of pharmacology2017
TC Mps1 12, a novel Mps1 inhibitor, suppresses the growth of hepatocellular carcinoma cells via the accumulation of chromosomal instability.
Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Chemical Genetics with SP600125 Reveals That Mps1 Protein Kinase Works as a Regulatory Element in Post-embryonic Development of theACS omega · 2025Article
- Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex.Nature communications · 2025Article
- TTK promotes HER2 + breast cancer cell migration, apoptosis, and resistance to targeted therapy by modulating the Akt/mTOR axis.Journal of cancer research and clinical oncology · 2024Article
- TTK/MPS1 inhibitor OSU-13 targets the mitotic checkpoint and is a potential therapeutic strategy for myeloma.Haematologica · 2024Article
- Comprehensively analyzing the genetic alterations, and identifying key genes in ovarian cancer.Oncology research · 2023Article
- Computational Biology Dynamics of Mps1 Kinase Molecular Interactions with Isoflavones Reveals a Chemical Scaffold with Potential to Develop New Therapeutics for the Treatment of Cancer.International journal of molecular sciences · 2022Article
- The spindle assembly checkpoint is a therapeutic vulnerability of CDK4/6 inhibitor-resistant ERScience advances · 2022Article
- Prognostic Value of Cancer-Associated Fibroblast-Related Gene Signatures in Hepatocellular Carcinoma.Frontiers in endocrinology · 2022Article
- Targeting Mps1 in combination with paclitaxel inhibits osteosarcoma progression by modulating spindle assembly checkpoint and Akt/mTOR signaling.Oncology letters · 2021Article
- Studies of Interaction Mechanism between Pyrido [3,4-Molecules (Basel, Switzerland) · 2021Article
- Integrated genomics and comprehensive validation reveal drivers of genomic evolution in esophageal adenocarcinoma.Communications biology · 2021Article
- Article
- Comprehensive Analysis of Gene Expression Changes and Validation in Hepatocellular Carcinoma.OncoTargets and therapy · 2021Article
- Data mining of immune-related prognostic genes in metastatic melanoma microenvironment.Bioscience reports · 2020Article
- Review
- TTK regulates proliferation and apoptosis of gastric cancer cells through the Akt-mTOR pathway.FEBS open bio · 2020Article
- TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination.The Journal of clinical investigation · 2020Article
- Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients.Journal of translational medicine · 2019Article
- Imbalance of the spindle-assembly checkpoint promotes spindle poison-mediated cytotoxicity with distinct kinetics.Cell death & disease · 2019Article
- Expression of cancer-testis antigens in esophageal cancer and their progress in immunotherapy.Journal of cancer research and clinical oncology · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeChromosomal instability is not only a hallmark of cancer but also an attractive therapeutic target. A diverse set of mitotic kinases maintains chromosomal stability. One of these is monopolar spindle 1 (Mps1, also known as TTK), which is essential for chromosome alignment and for the spindle assembly checkpoint (SAC). Pharmacological inhibition of Mps1 has been suggested as a cancer therapeutic; however, despite the existence of a novel Mps1 inhibitor, TC Mps1 12, no such studies have been performed. EXPERIMENTAL APPROACH: The effects of TC Mps1 12 on cell viability, chromosome alignment, centrosome number, mitotic duration, apoptosis and SAC were determined in hepatocellular carcinoma (HCC) cells. In addition, the association of Mps1 expression with the overall survival of HCC patients was analysed. KEY
resultsTreatment of human HCC cells with TC Mps1 12 led to chromosome misalignment and missegregation, and disorganization of centrosomes. Even in the presence of these errors, TC Mps1 12-treated cells overrode the SAC, resulting in a shortened mitotic duration and mitotic slippage. This mitotic catastrophe triggered apoptosis and, finally, inhibited the growth of HCC cells. In addition, the expression of the Mps1-encoding TTK gene was associated with poor overall survival of HCC patients. CONCLUSION AND IMPLICATIONS: TC Mps1 12 results in the accumulation of chromosomal instabilities and mitotic catastrophe in HCC cells. Overall, these data demonstrate that the inhibition of Mps1 kinase using TC Mps1 12 is a promising therapeutic approach for liver cancer.
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