Abstract
Y-box binding protein-1 (YB-1) is a proto-oncogenic protein associated with protein translation regulation. It plays a crucial role in the development and progression of triple-negative breast cancer (TNBC). In this study, we describe a promising approach to inhibit YB-1 using SU056, a small-molecule inhibitor. SU056 physically interacts with YB-1 and reduces its expression, which helps to restrain the progression of TNBC. Proteome profiling analysis indicates that the inhibition of YB-1 by SU056 can alter the proteins that regulate protein translation, an essential process for cancer cell growth. Preclinical studies on human cells, mice, and patient-derived xenograft tumor models show the effectiveness of SU056. Moreover, toxicological studies have shown that SU056 treatment and dosing are well tolerated without any adverse effects. Overall, our study provides a strong foundation for the further development of SU056 as a potential treatment option for patients with TNBC by targeting YB-1.
Original language | English (US) |
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Article number | 101552 |
Journal | Cell Reports Medicine |
Volume | 5 |
Issue number | 5 |
DOIs | |
State | Published - May 21 2024 |
Keywords
- CETSA
- RPL
- RPS
- YB-1
- eIF
- protein translation
- proteosome profiling
- ribosomes
- small molecule
- triple-negative breast cancer
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology