Roles of USP1 in Ewing sarcoma.

ABSTRACT: Ewing sarcoma is a cancer of bone and soft tissue in children and young adults that is driven by the EWS-ETS fusion transcription factor, most commonly EWS-FLI1. We previously reported that Ewing sarcoma harbors two populations of cells, the CD133^high population displaying higher growth rate and the CD133^low population displaying chemotherapy resistance. We now find that the ubiquitin-specific protease 1 (USP1) is a transcriptional target of the EWS-FLI1 fusion oncoprotein, expressed at high and low levels in the CD133^high and the CD133^low populations, respectively, and determines chemo-sensitivity. We also find that USP1 inhibits cdc42, increases EWS-FLI1 transcriptional output, and simulates Ewing sarcoma growth. We show that chemo-sensitizatio

SUBMITTER: Jayabal P 

PROVIDER: S-EPMC10843185 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature