Study uncovers critical roles for USP1 in Ewing sarcoma

A new research paper was published in Genes & Cancer on February 5, 2024, entitled, "Roles of USP1 in Ewing sarcoma."

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.

Researchers Panneerselvam Jayabal, Xiuye Ma and Yuzuru Shiio from The University of Texas Health Science Center 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. In their new study, the researchers 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. 

"Ubiquitin-specific protease 1 (USP1) is a deubiquitinating enzyme that plays important roles in DNA damage response."

They also found that USP1 inhibits cdc42, increases EWS-FLI1 transcriptional output, and simulates Ewing sarcoma growth. Results show that chemo-sensitization by USP1 is independent of cdc42. A pharmacological inhibitor of USP1 was able to activate cdc42 and inhibit Ewing sarcoma growth. 

"These results uncover critical roles for USP1 in Ewing sarcoma, which regulates growth and chemo-sensitivity via distinct mechanisms."