Evidence map›Paper›PMID 38357786›Full record

ArticleMolecular oncology2024

TPX2 overexpression promotes sensitivity to dasatinib in breast cancer by activating YAP transcriptional signaling.

Carlos Marugán, Natalia Sanz-Gómez, Beatriz Ortigosa, Ana Monfort-Vengut, Cristina Bertinetti, Ana Teijo, Marta González, Alicia Alonso de la Vega, María José Lallena, Gema Moreno-Bueno and 1 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.6field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 5 citations in OpenAlex.

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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

11 authors at 3 institutions in 1 country.

Carlos MarugánCell Cycle & Cancer Biomarkers Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, Madrid, Spain.ORCID 0009-0009-0820-0449
Natalia Sanz-GómezCell Cycle & Cancer Biomarkers Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, Madrid, Spain.ORCID 0000-0001-6826-7148
Beatriz OrtigosaCell Cycle & Cancer Biomarkers Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, Madrid, Spain.
Ana Monfort-VengutCell Cycle & Cancer Biomarkers Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, Madrid, Spain.ORCID 0000-0003-0096-1867
Cristina BertinettiCell Cycle & Cancer Biomarkers Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, Madrid, Spain.
Ana TeijoPathology Department, MD Anderson Cancer Center, Madrid, Spain.
Marta GonzálezCell Cycle & Cancer Biomarkers Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, Madrid, Spain.
Alicia Alonso de la VegaCell Cycle & Cancer Biomarkers Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, Madrid, Spain.ORCID 0000-0002-4898-6871
María José LallenaDiscovery Chemistry Research and Technology, Eli Lilly and Company, Madrid, Spain.
Gema Moreno-BuenoTranslational Cancer Research Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Alberto Sols-Morreale (IIBM) CSIC-UAM, Madrid, Spain.ORCID 0000-0002-5030-6687
Guillermo de CárcerCell Cycle & Cancer Biomarkers Laboratory, Cancer Department, Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) CSIC-UAM, Madrid, Spain.ORCID 0000-0002-3220-1785
Instituto de Investigaciones Biomédicas Sols-Morreale · ESEli Lilly (Spain) · ESMD Anderson Cancer Center Madrid · ES

Funding

Instituto de Salud Carlos III - CIBERONC CB16/12/00295Ministerio de Ciencia, Innovación, Agencia Estatal de Investigación MCIN/AEI/FEDER FJC2020-044620-IMinisterio de Ciencia, Innovación, Agencia Estatal de Investigación MCIN/AEI/FEDER PID2019-104644RB-I00Ministerio de Ciencia, Innovación, Agencia Estatal de Investigación MCIN/AEI/FEDER PID2021-125705OB-I00Ministerio de Ciencia, Innovación, Agencia Estatal de Investigación MCIN/AEI/FEDER PID2022-136854OB-I00Ministerio de Ciencia, Innovación, Agencia Estatal de Investigación MCIN/AEI/FEDER RTI2018-095496-B-I00Spanish Association Against Cancer (AECC) Scientific Foundation LABAE16017DECASpanish Association Against Cancer (AECC) Scientific Foundation POSTD234371SANZSpanish Association Against Cancer (AECC) Scientific Foundation PROYE19036MORSpanish National Research Council (CSIC) 2018-20I114Spanish National Research Council (CSIC) 2021-AEP035Spanish National Research Council (CSIC) 2022-20I018
6 · The paper itself

Abstract

Chromosomal instability (CIN) is a hallmark of cancer aggressiveness, providing genetic plasticity and tumor heterogeneity that allows the tumor to evolve and adapt to stress conditions. CIN is considered a cancer therapeutic biomarker because healthy cells do not exhibit CIN. Despite recent efforts to identify therapeutic strategies related to CIN, the results obtained have been very limited. CIN is characterized by a genetic signature where a collection of genes, mostly mitotic regulators, are overexpressed in CIN-positive tumors, providing aggressiveness and poor prognosis. We attempted to identify new therapeutic strategies related to CIN genes by performing a drug screen, using cells that individually express CIN-associated genes in an inducible manner. We find that the overexpression of targeting protein for Xklp2 (TPX2) enhances sensitivity to the proto-oncogene c-Src (SRC) inhibitor dasatinib due to activation of the Yes-associated protein 1 (YAP) pathway. Furthermore, using breast cancer data from The Cancer Genome Atlas (TCGA) and a cohort of cancer-derived patient samples, we find that both TPX2 overexpression and YAP activation are present in a significant percentage of cancer tumor samples and are associated with poor prognosis; therefore, they are putative biomarkers for selection for dasatinib therapy.

Indexed as

Adaptor Proteins, Signal TransducingBreast NeoplasmsCell Cycle ProteinsDasatinibMicrotubule-Associated ProteinsProto-Oncogene MasSignal TransductionTranscription FactorsYAP-Signaling ProteinsCell Line, TumorDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticHumansNuclear ProteinsPhosphoproteinsAdaptor Proteins, Signal TransducingCell Cycle ProteinsDasatinibMAS1 protein, humanMicrotubule-Associated ProteinsNuclear ProteinsPhosphoproteinsProto-Oncogene MasTPX2 protein, humanTranscription FactorsYAP1 protein, humanYAP-Signaling Proteinschromosomal instabilitydasatinibHippo‐YAP/TAZmitosisSFK kinasesTPX2

Identifiers

PMID38357786
PMCPMC11161735
OpenAlexW4391840948

What OpenQuestion holds

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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.