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Negative correlation of single-cell PAX3:FOXO1 expression with tumorigenicity in rhabdomyosarcoma

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Item Type:Article
Title:Negative correlation of single-cell PAX3:FOXO1 expression with tumorigenicity in rhabdomyosarcoma
Creators Name:Regina, C. and Hamed, E. and Andrieux, G. and Angenendt, S. and Schneider, M. and Ku, M. and Follo, M. and Wachtel, M. and Ke, E. and Kikuchi, K. and Henssen, A.G. and Schäfer, B.W. and Boerries, M. and Wagers, A.J. and Keller, C. and Hettmer, S.
Abstract:Rhabdomyosarcomas (RMS) are phenotypically and functionally heterogeneous. Both primary human RMS cultures and low-passage Myf6Cre,Pax3:Foxo1,p53 mouse RMS cell lines, which express the fusion oncoprotein Pax3:Foxo1 and lack the tumor suppressor Tp53 (Myf6Cre,Pax3:Foxo1,p53), exhibit marked heterogeneity in PAX3:FOXO1 (P3F) expression at the single cell level. In mouse RMS cells, P3F expression is directed by the Pax3 promoter and coupled to eYFP. YFP(low)/P3F(low) mouse RMS cells included 87% G0/G1 cells and reorganized their actin cytoskeleton to produce a cellular phenotype characterized by more efficient adhesion and migration. This translated into higher tumor-propagating cell frequencies of YFP(low)/P3F(low) compared with YFP(high)/P3F(high) cells. Both YFP(low)/P3F(low) and YFP(high)/P3F(high) cells gave rise to mixed clones in vitro, consistent with fluctuations in P3F expression over time. Exposure to the anti-tropomyosin compound TR100 disrupted the cytoskeleton and reversed enhanced migration and adhesion of YFP(low)/P3F(low) RMS cells. Heterogeneous expression of PAX3:FOXO1 at the single cell level may provide a critical advantage during tumor progression.
Keywords:Animal Disease Models, Apoptosis, Computational Biology, Disease Susceptibility, Fusion Oncogene Proteins, Gene Expression Profiling, Immunophenotyping, Molecular Sequence Annotation, Neoplastic Cell Transformation, Neoplastic Gene Expression Regulation, Paired Box Transcription Factors, Rhabdomyosarcoma, Single-Cell Analysis, Tumor Cell Line, Animals, Mice
Source:Life Science Alliance
Publisher:Life Science Alliance
Page Range:e202001002
Date:September 2021
Official Publication:https://doi.org/10.26508/lsa.202001002
PubMed:View item in PubMed

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