Negative correlation of single-cell PAX3:FOXO1 expression with tumorigenicity in rhabdomyosarcoma
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. 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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Life science alliance. - 4, 9 (2021) , e202001002, ISSN: 2575-1077
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
-
Universität
- (wann)
-
2021
- Urheber
-
Regina, Carla
Hamed, Ebrahem
Geoffroy, Andrieux
Angenendt, Sina
Schneider, Michaela
Ku, Manching
Follo, Marie
Wachtel, Marco
Ke, Eugene
Kikuchi, Ken
Henssen, Anton George
Schäfer, Beat Werner
Börries, Melanie
Wagers, Amy J.
Keller, Charles
Hettmer, Simone
- DOI
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10.26508/lsa.202001002
- URN
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urn:nbn:de:bsz:25-freidok-2195096
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
15.08.2025, 07:39 MESZ
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Beteiligte
- Regina, Carla
- Hamed, Ebrahem
- Geoffroy, Andrieux
- Angenendt, Sina
- Schneider, Michaela
- Ku, Manching
- Follo, Marie
- Wachtel, Marco
- Ke, Eugene
- Kikuchi, Ken
- Henssen, Anton George
- Schäfer, Beat Werner
- Börries, Melanie
- Wagers, Amy J.
- Keller, Charles
- Hettmer, Simone
- Universität
Entstanden
- 2021
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