USP1 Expression Driven by EWS::FLI1 Transcription Factor Stabilizes Survivin and Mitigates Replication Stress in Ewing Sarcoma

• Published in: Molecular cancer research Vol. 21; no. 11; pp. 1186 - 1204
• Main Authors: Mallard, Halle J, Wan, Shibiao, Nidhi, Prakriti, Hanscom-Trofy, Yvan D, Mohapatra, Bhopal, Woods, Nicholas T, Lopez-Guerrero, Jose Antonio, Llombart-Bosch, Antonio, Machado, Isidro, Scotlandi, Katia, Kreiling, Natasha F, Perry, Megan C, Mirza, Sameer, Coulter, Donald W, Band, Vimla, Band, Hamid, Ghosal, Gargi
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01.11.2023
• Subjects: Cell Death And Senescence; Cell Line, Tumor; Cellular Stress Responses; Child; Dna Damage And Repair; Drug Mechanisms; Endogenous Risk Factors; Gene Expression Regulation, Neoplastic; Genome Maintenance; Humans; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Oncogenes & Tumor Suppressors; Pediatric Cancers; Proto-Oncogene Protein c-fli-1 - genetics; Proto-Oncogene Protein c-fli-1 - metabolism; RNA-Binding Protein EWS - genetics; RNA-Binding Protein EWS - metabolism; Sarcoma, Ewing - metabolism; Survivin - genetics; Survivin - metabolism; Ubiquitin-Specific Proteases - metabolism

In this study, we identify USP1 as a transcriptional target of EWS::FLI1 and demonstrate the requisite function of USP1 in Ewing sarcoma (EWS) cell survival in response to endogenous replication stress. EWS::FLI1 oncogenic transcription factor drives most EWS, a pediatric bone cancer. EWS cells disp...