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

Authors

  • C. Regina
  • E. Hamed
  • G. Andrieux
  • S. Angenendt
  • M. Schneider
  • M. Ku
  • M. Follo
  • M. Wachtel
  • E. Ke
  • K. Kikuchi
  • A.G. Henssen
  • B.W. Schäfer
  • M. Boerries
  • A.J. Wagers
  • C. Keller
  • S. Hettmer

Journal

  • Life Science Alliance

Citation

  • Life Sci Alliance 4 (9): e202001002

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.


DOI

doi:10.26508/lsa.202001002