Data from The DRAP1/DR1 Repressor Complex Increases mTOR Activity to Promote Progression and Confer Everolimus Sensitivity in Triple-Negative Breast Cancer

• DOI: 10.1158/0008-5472.c.7403526
• Publication Date: 2024-08-15T07:31:06Z
• Authors: Min-Ying Huang; Shu-Yuan Hu; Jia Dong; Ling Deng; Lisa Andriani; Xiao-Yan Ma; Yin-Ling Zhang; Fang-Lin Zhang; Zhi-Ming Shao; Da-Qiang Li
• Keywords: Triple-negative breast cancer; Corepressor

<div>Abstract<p>Triple-negative breast cancer (TNBC) is the most aggressive subtype of cancer. Transcriptional dysregulation a hallmark cancer, and several transcriptional regulators have been demonstrated to contribute progression. In this study, we identified an upregulation corepressor downregulator transcription 1–associated protein 1 (DRAP1) in TNBC, which was closely associated with poor recurrence-free survival patients TNBC. DRAP1 promoted TNBC proliferation, migration, invasion <i>in vitro</i> tumor growth metastasis vivo</i>. Mechanistically, (DR1)/DRAP1 heterodimer complex inhibited expression cytosolic arginine sensor for mTORC1 subunit (CASTOR1) thereby increased activation mTOR, sensitized treatment mTOR inhibitor everolimus. DR1 also formed positive feedback loop. enhanced stability by recruiting deubiquitinase USP7 inhibit its proteasomal degradation; turn, directly transcription. Collectively, study uncovered DRAP1–DR1 bidirectional regulatory pathway that promotes progression, suggesting targeting DRAP1/DR1 might be potential therapeutic strategy treat TNBC.</p><p><b>Significance:</b> form loop repressor cooperatively stimulate signaling, leading progression everolimus sensitivity triple-negative cancer.</p></div>