{"doi":"10.26508/lsa.202001002","title":"Negative correlation of single-cell <i>PAX3:FOXO1</i> 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 . 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.","journal":"Life Science Alliance","year":2021,"id":182785,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":735287,"name":"Ebrahem Hamed","orcid":"0000-0002-3595-677X","position":1,"is_corresponding":false},{"id":17189,"name":"Geoffroy Andrieux","orcid":"0000-0002-5389-9481","position":2,"is_corresponding":false},{"id":735288,"name":"Sina Angenendt","orcid":"0000-0003-0827-7613","position":3,"is_corresponding":false},{"id":735773,"name":"Michaela Schneider","orcid":null,"position":4,"is_corresponding":false},{"id":6479,"name":"Manching Ku","orcid":"0000-0001-5168-4308","position":5,"is_corresponding":false},{"id":735289,"name":"Marie Follo","orcid":"0000-0002-3090-7442","position":6,"is_corresponding":false},{"id":316691,"name":"Marco Wachtel","orcid":"0000-0002-6077-3692","position":7,"is_corresponding":false},{"id":531892,"name":"Eugene Ke","orcid":"0000-0002-6369-5802","position":8,"is_corresponding":false},{"id":735290,"name":"Ken Kikuchi","orcid":"0000-0003-3097-7480","position":9,"is_corresponding":false},{"id":110037,"name":"Anton G. Henssen","orcid":"0000-0003-1534-778X","position":10,"is_corresponding":false},{"id":316692,"name":"Beat W. Schäfer","orcid":"0000-0001-5988-2915","position":11,"is_corresponding":false},{"id":5620,"name":"Melanie Boerries","orcid":"0000-0002-3670-0602","position":12,"is_corresponding":false},{"id":59412,"name":"Amy J. Wagers","orcid":"0000-0002-0066-0485","position":13,"is_corresponding":false},{"id":439287,"name":"Charles Keller","orcid":"0000-0003-2505-7487","position":14,"is_corresponding":false},{"id":236622,"name":"Simone Hettmer","orcid":"0000-0003-1709-4448","position":15,"is_corresponding":false},{"id":735772,"name":"Carla Regina","orcid":null,"position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:48:13.605421Z","pmid":"34187933","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}