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Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
Published on: June 27, 2020
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Roles of USP1 in Ewing sarcoma
Panneerselvam Jayabal1, Xiuye Ma1, Yuzuru Shiio1,2,3
1Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229, USA.
Genes & Cancer
|February 7, 2024
Summary
Ubiquitin-specific protease 1 (USP1) drives Ewing sarcoma growth and chemo-resistance by regulating EWS-FLI1 and cdc42. Inhibiting USP1 shows therapeutic potential for treating this pediatric cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Ewing sarcoma is a pediatric bone and soft tissue cancer driven by EWS-ETS fusions, notably EWS-FLI1.
- Ewing sarcoma cells exist as two populations: CD133high (high growth) and CD133low (chemo-resistant).
Purpose of the Study:
- To investigate the role of ubiquitin-specific protease 1 (USP1) in Ewing sarcoma growth and chemo-sensitivity.
- To explore USP1's relationship with EWS-FLI1 and cdc42 in different Ewing sarcoma cell populations.
Main Methods:
- Analysis of USP1 expression in CD133high and CD133low Ewing sarcoma cells.
- Investigating USP1's effect on EWS-FLI1 transcriptional activity and cdc42.
- Utilizing a pharmacological USP1 inhibitor to assess its impact on Ewing sarcoma growth and chemo-sensitivity.
Main Results:
- USP1 is a transcriptional target of EWS-FLI1, with differential expression in CD133high and CD133low cells.
- USP1 promotes Ewing sarcoma growth by increasing EWS-FLI1 output and inhibiting cdc42.
- USP1-mediated chemo-sensitization is independent of cdc42.
- USP1 inhibition activates cdc42 and reduces Ewing sarcoma growth.
Conclusions:
- USP1 plays a dual role in Ewing sarcoma, regulating both tumor growth and chemo-sensitivity through distinct mechanisms.
- Targeting USP1 offers a potential therapeutic strategy for Ewing sarcoma, impacting both tumor proliferation and treatment response.
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