Negative correlation of single-cell PAX3:FOXO1 expression with tumorigenicity in rhabdomyosarcoma
Copyright policy )Negative correlation of single-cell PAX3:FOXO1 expression with tumorigenicity in rhabdomyosarcoma
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. YFPlow/P3Flow 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 YFPlow/P3Flow compared with YFPhigh/P3Fhigh cells. Both YFPlow/P3Flow and YFPhigh/P3Fhigh 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 YFPlow/P3Flow RMS cells. Heterogeneous expression of PAX3:FOXO1 at the single cell level may provide a critical advantage during tumor progression.
- Harvard Stem Cell Institute, Cambridge, MA, USA United States
- Deutsches Konsortium für Translationale Krebsforschung Germany
- University of Zurich Switzerland
- Harvard University United States
- Boston Children's Hospital United States
Cancer Research, Oncogene Proteins, Fusion, 610, 610 Medicine & health, Apoptosis, 1301 Biochemistry, Genetics and Molecular Biology (miscellaneous), Immunophenotyping, Mice, Cell Line, Tumor, 1110 Plant Science, 2307 Health, Toxicology and Mutagenesis, Rhabdomyosarcoma, Animals, Humans, Paired Box Transcription Factors, 610 Medicine & health, Research Articles, Gene Expression Profiling, Computational Biology, Molecular Sequence Annotation, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Cell Transformation, Neoplastic, 10036 Medical Clinic, Disease Susceptibility, Single-Cell Analysis, 2303 Ecology, Topic 2: Molecular Processes and Therapies
Cancer Research, Oncogene Proteins, Fusion, 610, 610 Medicine & health, Apoptosis, 1301 Biochemistry, Genetics and Molecular Biology (miscellaneous), Immunophenotyping, Mice, Cell Line, Tumor, 1110 Plant Science, 2307 Health, Toxicology and Mutagenesis, Rhabdomyosarcoma, Animals, Humans, Paired Box Transcription Factors, 610 Medicine & health, Research Articles, Gene Expression Profiling, Computational Biology, Molecular Sequence Annotation, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Cell Transformation, Neoplastic, 10036 Medical Clinic, Disease Susceptibility, Single-Cell Analysis, 2303 Ecology, Topic 2: Molecular Processes and Therapies
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