In:
Life Science Alliance, Life Science Alliance, LLC, Vol. 4, No. 9 ( 2021-09), p. e202001002-
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
2575-1077
DOI:
10.26508/lsa.202001002
Sprache:
Englisch
Verlag:
Life Science Alliance, LLC
Publikationsdatum:
2021
ZDB Id:
2948687-7