ArticleOncotarget2016
Whole-genome duplication increases tumor cell sensitivity to MPS1 inhibition.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Mitochondrial Adaptations Underlying Tetraploidization in Human Cancer, Fungal, and Yeast Models.Biology · 2026Article
- Yeast with elevated chromosome numbers are addicted to high levels of Mps1.bioRxiv : the preprint server for biology · 2025Article
- Comparative Pharmacological Analysis of Mitotic Inhibitors Using Isogenic Ploidy Series of HAP1 Cells.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination.Frontiers in oncology · 2024Article
- Whole-genome doubling in tissues and tumors.Trends in genetics : TIG · 2023Review
- Tetraploidy-linked sensitization to CENP-E inhibition in human cells.Molecular oncology · 2023Article
- Identification of prognostic biomarkers in papillary renal cell carcinoma and PTTG1 may serve as a biomarker for predicting immunotherapy response.Annals of medicine · 2022Article
- Studies of Interaction Mechanism between Pyrido [3,4-Molecules (Basel, Switzerland) · 2021Article
- Article
- Gross genetic alterations and genetic heterogeneity in a periductal stromal tumor of the breast.Molecular cytogenetics · 2020Article
- Inhibition of mitotic kinase Mps1 promotes cell death in neuroblastoma.Scientific reports · 2020Article
- Tetraploidy-Associated Genetic Heterogeneity Confers Chemo-Radiotherapy Resistance to Colorectal Cancer Cells.Cancers · 2020Article
- Imbalance of the spindle-assembly checkpoint promotes spindle poison-mediated cytotoxicity with distinct kinetics.Cell death & disease · 2019Article
- Drug-induced aneuploidy and polyploidy is a mechanism of disease relapse in MYC/BCL2-addicted diffuse large B-cell lymphoma.Oncotarget · 2018Article
- Article
- Ancestral Genome Reconstruction on Whole Genome Level.Current genomics · 2017Review
- Stable aneuploid tumors cells are more sensitive to TTK inhibition than chromosomally unstable cell lines.Oncotarget · 2017Article
- TC Mps1 12, a novel Mps1 inhibitor, suppresses the growth of hepatocellular carcinoma cells via the accumulation of chromosomal instability.British journal of pharmacology · 2017Article
- Caspase 2 in mitotic catastrophe: The terminator of aneuploid and tetraploid cells.Molecular & cellular oncology · 2017Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several lines of evidence indicate that whole-genome duplication resulting in tetraploidy facilitates carcinogenesis by providing an intermediate and metastable state more prone to generate oncogenic aneuploidy. Here, we report a novel strategy to preferentially kill tetraploid cells based on the abrogation of the spindle assembly checkpoint (SAC) via the targeting of TTK protein kinase (better known as monopolar spindle 1, MPS1). The pharmacological inhibition as well as the knockdown of MPS1 kills more efficiently tetraploid cells than their diploid counterparts. By using time-lapse videomicroscopy, we show that tetraploid cells do not survive the aborted mitosis due to SAC abrogation upon MPS1 depletion. On the contrary diploid cells are able to survive up to at least two more cell cycles upon the same treatment. This effect might reflect the enhanced difficulty of cells with whole-genome doubling to tolerate a further increase in ploidy and/or an elevated level of chromosome instability in the absence of SAC functions. We further show that MPS1-inhibited tetraploid cells promote mitotic catastrophe executed by the intrinsic pathway of apoptosis, as indicated by the loss of mitochondrial potential, the release of the pro-apoptotic cytochrome c from mitochondria, and the activation of caspases. Altogether, our results suggest that MPS1 inhibition could be used as a therapeutic strategy for targeting tetraploid cancer cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.