Evidence map›Paper›PMID 23700430›Full record

ArticlePloS one2013

TTK/hMPS1 is an attractive therapeutic target for triple-negative breast cancer.

Virginie Maire, Céline Baldeyron, Marion Richardson, Bruno Tesson, Anne Vincent-Salomon, Eléonore Gravier, Bérengère Marty-Prouvost, Leanne De Koning, Guillem Rigaill, Aurélie Dumont and 8 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
4.4field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  12. CD8Molecular medicine reports · 2024
    Article
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  16. Seize the engine: Emerging cell cycle targets in breast cancer.Clinical and translational medicine · 2024
    Review
  17. Article
  18. Article
  19. Article
  20. Article

32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 1 country.

Virginie MaireInstitut Curie, Research Center, Paris, France ; Breast Cancer Biology Group, Department of Translational Research, Paris, France.
Céline Baldeyron
Marion Richardson
Bruno Tesson
Anne Vincent-Salomon
Eléonore Gravier
Bérengère Marty-Prouvost
Leanne De Koning
Guillem Rigaill
Aurélie Dumont
David Gentien
Emmanuel Barillot
Sergio Roman-Roman
Stéphane Depil
Francisco Cruzalegui
Alain Pierré
Gordon C Tucker
Thierry Dubois
Institut Curie · FRAVL (France) · FRTranslational Research in Oncology · FRÉcole Nationale Supérieure des Mines de Paris · FRInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) represents a subgroup of breast cancers (BC) associated with the most aggressive clinical behavior. No targeted therapy is currently available for the treatment of patients with TNBC. In order to discover potential therapeutic targets, we searched for protein kinases that are overexpressed in human TNBC biopsies and whose silencing in TNBC cell lines causes cell death. A cohort including human BC biopsies obtained at Institut Curie as well as normal tissues has been analyzed at a gene-expression level. The data revealed that the human protein kinase monopolar spindle 1 (hMPS1), also known as TTK and involved in mitotic checkpoint, is specifically overexpressed in TNBC, compared to the other BC subgroups and healthy tissues. We confirmed by immunohistochemistry and reverse phase protein array that TNBC expressed higher levels of TTK protein compared to the other BC subgroups. We then determined the biological effects of TTK depletion by RNA interference, through analyses of tumorigenic capacity and cell viability in different human TNBC cell lines. We found that RNAi-mediated depletion of TTK in various TNBC cell lines severely compromised their viability and their ability to form colonies in an anchorage-independent manner. Moreover, we observed that TTK silencing led to an increase in H2AX phosphorylation, activation of caspases 3/7, sub-G1 cell population accumulation and high annexin V staining, as well as to a decrease in G1 phase cell population and an increased aneuploidy. Altogether, these data indicate that TTK depletion in TNBC cells induces apoptosis. These results point out TTK as a protein kinase overexpressed in TNBC that may represent an attractive therapeutic target specifically for this poor prognosis associated subgroup of breast cancer.

Indexed as

ApoptosisCaspase 3Caspase 7Cell Cycle CheckpointsCell Cycle ProteinsCell Line, TumorCell SurvivalDisease-Free SurvivalFemaleGene Knockdown TechniquesHumansKaplan-Meier EstimateMolecular Targeted TherapyProportional Hazards ModelsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesCASP3 protein, humanCASP7 protein, humanCaspase 3Caspase 7Cell Cycle ProteinsProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProteomeRNA, Small InterferingTTK protein, human

Identifiers

PMID23700430
PMCPMC3658982
OpenAlexW1987347990

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Registered trials

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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.