ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2011
Identifying inhibitors of epithelial-mesenchymal transition by connectivity map-based systems approach.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 63 citations in OpenAlex.
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- Transcriptomic-Driven Drug Repurposing Reveals SP600125 as a Promising Drug Candidate for the Treatment of Glial-Mesenchymal Transition in Glioblastoma.International journal of molecular sciences · 2025Article
- Genome-scale modeling identifies dynamic metabolic vulnerabilities during the epithelial to mesenchymal transition.Communications biology · 2024Article
- Systematic computational strategies for identifying protein targets and lead discovery.RSC medicinal chemistry · 2024Review
- Systemic sclerosis biomarkers detection in the secretome of TGFβ1-activated primary human lung fibroblasts.Journal of proteomics · 2021Article
- Effective Drug Concentration and Selectivity Depends on Fraction of Primitive Cells.International journal of molecular sciences · 2021Article
- miR-944 Suppresses EGF-Induced EMT in Colorectal Cancer Cells by Directly Targeting GATA6.OncoTargets and therapy · 2021Article
- Recent Advances in Cancer Plasticity: Cellular Mechanisms, Surveillance Strategies, and Therapeutic Optimization.Frontiers in oncology · 2020Review
- Reversal of Epithelial-Mesenchymal Transition by Natural Anti-Inflammatory and Pro-Resolving Lipids.Cancers · 2019Review
- Defining Protein Pattern Differences Among Molecular Subtypes of Diffuse Gliomas Using Mass Spectrometry.Molecular & cellular proteomics : MCP · 2019Article
- Crosstalk between autophagy and epithelial-mesenchymal transition and its application in cancer therapy.Molecular cancer · 2019Review
- Statins may have double-edged effects in patients with lung adenocarcinoma after lung resection.Cancer management and research · 2019Article
- Phthalazinone Pyrazole Enhances the Hepatic Functions of Human Embryonic Stem Cell-Derived Hepatocyte-Like Cells via Suppression of the Epithelial-Mesenchymal Transition.Stem cell reviews and reports · 2018Article
- Epithelial-mesenchymal transition leads to NK cell-mediated metastasis-specific immunosurveillance in lung cancer.The Journal of clinical investigation · 2018Article
- Cellular Phenotype Plasticity in Cancer Dormancy and Metastasis.Frontiers in oncology · 2018Review
- Metformin sensitizes hypoxia-induced gefitinib treatment resistance of HNSCC via cell cycle regulation and EMT reversal.Cancer management and research · 2018Article
- Review
- FSIP1 binds HER2 directly to regulate breast cancer growth and invasiveness.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Therapeutic Targeting of Epithelial Plasticity Programs: Focus on the Epithelial-Mesenchymal Transition.Cells, tissues, organs · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAcquisition of mesenchymal phenotype by epithelial cells by means of epithelial-mesenchymal transition (EMT) is considered as an early event in the multistep process of tumor metastasis. Therefore, inhibition of EMT might be a rational strategy to prevent metastasis.
methodsUsing the global gene expression profile from a cell culture model of transforming growth factor-β (TGF-β)-induced EMT, we identified potential EMT inhibitors. We used a publicly available database (www.broad.mit.edu/cmap) comprising gene expression profiles obtained from multiple different cell lines in response to various drugs to derive negative correlations to EMT gene expression profile using Connectivity Map, a pattern matching tool.
resultsExperimental validation of the identified compounds showed rapamycin as a novel inhibitor of TGF-β signaling along with 17-AAG, a known modulator of TGF-β pathway. Both of these compounds completely blocked EMT and the associated migratory and invasive phenotype. The other identified compound, LY294002, demonstrated a selective inhibition of mesenchymal markers, cell migration and invasion, without affecting the loss of E-cadherin expression or Smad phosphorylation.
conclusionsOur data reveal that rapamycin is a novel modulator of TGF-β signaling, and along with 17-AAG and LY294002, could be used as therapeutic agent for inhibiting EMT. This study demonstrates the potential of a systems approach in identifying novel modulators of a complex biological process.
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Registered trials
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