A logical model of Ewing sarcoma cell epithelial-to-mesenchymal transition supports the existence of hybrid cellular phenotypes.
Daner A SilveiraShantanu GuptaMariane da Cunha JaegerCaroline Brunetto de FariasJosé Carlos Merino MombachMarialva SinigagliaPublished in: FEBS letters (2023)
Ewing sarcoma (ES) is a highly aggressive pediatric tumor driven by the RNA-binding protein EWS (EWS)/friend leukemia integration 1 transcription factor (FLI1) chimeric transcription factor, which is involved in epithelial-mesenchymal transition (EMT). EMT stabilizes a hybrid cell state, boosting metastatic potential and drug resistance. Nevertheless, the mechanisms underlying the maintenance of this hybrid phenotype in ES remain elusive. Our study proposes a logical EMT model for ES, highlighting zinc finger E-box-binding homeobox 2 (ZEB2), miR-145 and miR-200 circuits that maintain hybrid states. The model aligns with experimental findings and reveals a previously unknown circuit supporting the mesenchymal phenotype. These insights emphasize the role of ZEB2 in the maintenance of the hybrid state in ES.
Keyphrases
- epithelial mesenchymal transition
- transcription factor
- binding protein
- long non coding rna
- transforming growth factor
- cell therapy
- signaling pathway
- cell proliferation
- dna binding
- single cell
- bone marrow
- small cell lung cancer
- squamous cell carcinoma
- stem cells
- long noncoding rna
- mesenchymal stem cells
- climate change