ArticleMolecular oncology2014
TP53 mutation-correlated genes predict the risk of tumor relapse and identify MPS1 as a potential therapeutic kinase in TP53-mutated breast cancers.
Article in Molecular oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 87 citations in OpenAlex.
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- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- Bioinformatics-Driven Investigations of Signature Biomarkers for Triple-Negative Breast Cancer.Bioinformatics and biology insights · 2025Article
- Atherosclerosis-related biomarker PABPC1 predicts pan-cancer events.Stroke and vascular neurology · 2024Article
- Cancer testis antigens: Emerging therapeutic targets leveraging genomic instability in cancer.Molecular therapy. Oncology · 2024Review
- BID expression determines the apoptotic fate of cancer cells after abrogation of the spindle assembly checkpoint by AURKB or TTK inhibitors.Molecular cancer · 2023Article
- ESRP1-regulated isoform switching of LRRFIP2 determines metastasis of gastric cancer.Nature communications · 2022Article
- Identification of Candidate Genes in Breast Cancer Induced by Estrogen Plus Progestogens Using Bioinformatic Analysis.International journal of molecular sciences · 2022Article
- gp130 Cytokines Activate Novel Signaling Pathways and Alter Bone Dissemination in ER+ Breast Cancer Cells.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Quantitative Analysis of TP53-Related Lung Cancer Based on Radiomics.International journal of general medicine · 2022Article
- Clinical implication of genetic composition and molecular mechanism on treatment strategies of HER2-positive breast cancers.Frontiers in oncology · 2022Review
- M6A associated TSUC7 inhibition contributed to Erlotinib resistance in lung adenocarcinoma through a notch signaling activation dependent way.Journal of experimental & clinical cancer research : CR · 2021Article
- Integrated bioinformatics analysis to identify key genes related to the prognosis of esophageal squamous cell carcinoma.Translational cancer research · 2021Article
- Neddylation Regulates Macrophages and Implications for Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Identification of a Four-Gene Signature With Prognostic Significance in Endometrial Cancer Using Weighted-Gene Correlation Network Analysis.Frontiers in genetics · 2021Article
- HER2 splice variants in breast cancer: investigating their impact on diagnosis and treatment outcomes.Oncotarget · 2020Review
- Mir-20a-5p induced WTX deficiency promotes gastric cancer progressions through regulating PI3K/AKT signaling pathway.Journal of experimental & clinical cancer research : CR · 2020Article
- Modulation of Mutational Landscape in HER2-Positive Breast Cancer after Neoadjuvant Chemotherapy.Translational oncology · 2020Article
- MeCP2 facilitates breast cancer growth via promoting ubiquitination-mediated P53 degradation by inhibiting RPL5/RPL11 transcription.Oncogenesis · 2020Article
Corrections and comments
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Authors and funding
16 authors at 11 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancers (BC) carry a complex set of gene mutations that can influence their gene expression and clinical behavior. We aimed to identify genes driven by the TP53 mutation status and assess their clinical relevance in estrogen receptor (ER)-positive and ER-negative BC, and their potential as targets for patients with TP53 mutated tumors. Separate ROC analyses of each gene expression according to TP53 mutation status were performed. The prognostic value of genes with the highest AUC were assessed in a large dataset of untreated, and neoadjuvant chemotherapy treated patients. The mitotic checkpoint gene MPS1 was the most significant gene correlated with TP53 status, and the most significant prognostic marker in all ER-positive BC datasets. MPS1 retained its prognostic value independently from the type of treatment administered. The biological functions of MPS1 were investigated in different BC cell lines. We also assessed the effects of a potent small molecule inhibitor of MPS1, SP600125, alone and in combination with chemotherapy. Consistent with the gene expression profiling and siRNA assays, the inhibition of MPS1 by SP600125 led to a reduction in cell viability and a significant increase in cell death, selectively in TP53-mutated BC cells. Furthermore, the chemical inhibition of MPS1 sensitized BC cells to conventional chemotherapy, particularly taxanes. Our results collectively demonstrate that TP53-correlated kinase MPS1, is a potential therapeutic target in BC patients with TP53 mutated tumors, and that SP600125 warrant further development in future clinical trials.
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