Data from USP9X Downregulation Renders Breast Cancer Cells Resistant to Tamoxifen

• DOI: 10.1158/0008-5472.c.6505985
• Publication Date: 2023-03-31T23:15:34Z
• Authors: Hendrika M. Ooste...; E. Marielle Hijmans; Thijn R. Brummelkamp; Sander Canisius; Lodewyk F.A. Wessels; Wilbert Zwart; René Bernards
• Keywords: Fulvestrant; Antiestrogen

<div>Abstract<p>Tamoxifen is one of the most widely used endocrine agents for treatment estrogen receptor α (ERα)–positive breast cancer. Although effective in patients, resistance to tamoxifen a clinically significant problem and mechanisms responsible remain elusive. To address this problem, we performed large scale loss-of-function genetic screen ZR-75-1 luminal cancer cells identify candidate genes. In manner, found that loss function deubiquitinase USP9X prevented proliferation arrest by tamoxifen, but not ER downregulator fulvestrant. RNAi-mediated attenuation was sufficient stabilize ERα on chromatin presence causing global tamoxifen-driven activation ERα-responsive Using gene signature defined their differential expression after were able define patients with ERα-positive experiencing poor outcome adjuvant tamoxifen. The specific its lack correlation survival who did receive therapy. Overall, our findings as biomarker response <i>Cancer Res; 74(14); 3810–20. ©2014 AACR</i>.</p></div>