PT  - JOURNAL ARTICLE
AU  - Carla Regina
AU  - Ebrahem Hamed
AU  - Geoffroy Andrieux
AU  - Sina Angenendt
AU  - Michaela Schneider
AU  - Manching Ku
AU  - Marie Follo
AU  - Marco Wachtel
AU  - Eugene Ke
AU  - Ken Kikuchi
AU  - Anton G Henssen
AU  - Beat W Schäfer
AU  - Melanie Boerries
AU  - Amy J Wagers
AU  - Charles Keller
AU  - Simone Hettmer
TI  - Negative correlation of single-cell <em>PAX3:FOXO1</em> expression with tumorigenicity in rhabdomyosarcoma
AID  - 10.26508/lsa.202001002
DP  - 2021 Sep 01
TA  - Life Science Alliance
PG  - e202001002
VI  - 4
IP  - 9
4099  - https://www.life-science-alliance.org/content/4/9/e202001002.short
4100  - https://www.life-science-alliance.org/content/4/9/e202001002.full
SO  - Life Sci. Alliance2021 Sep 01; 4
AB  - 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.