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 CD133high population displaying higher growth rate and the CD133low 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 CD133high and the CD133low 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.”

Source: Impact Jounrnals LLC