Synergistic regulation of DACH1 stability by acetylation and deubiquitination promotes colorectal cancer progression by Liang Zhu & Can Cheng & Heng Li & Jingwen Liu & Yang Wu & Liang Wu & Hanhui Yao instant download

Synergistic regulation of DACH1 stability by acetylation and deubiquitination promotes colorectal cancer progression by Liang Zhu & Can Cheng & Heng Li & Jingwen Liu & Yang Wu & Liang Wu & Hanhui Yao instant download

Colorectal cancer (CRC) remains a significant challenge in oncology, with limited therapeutic options for aggressive subtypes. Thisstudy elucidates the critical roles of USP7 and DACH1 in CRC, revealing their involvement in tumor progression and potential astherapeutic targets. USP7 was identified as a deubiquitinase that stabilizes DACH1, enhancing its tumor-promoting activities.Mechanistically, USP7 directly interacts with DACH1, protecting DACH1 from UHRF1-induced ubiquitination and degradation byremoving ubiquitin chains, particularly K48-linked types, which are crucial for protein degradation. Additionally, acetylation at K680on DACH1, mediated by acetyltransferase GCN5, enhances its interaction with USP7, further influencing DACH1 stability andfunction. Clinically, high levels of USP7 and DACH1 correlate with poor prognosis in CRC patients, underscoring their significance indisease progression. These findings suggest that targeting the USP7-DACH1 axis could offer a novel therapeutic strategy for1234567890();,:managing CRC, particularly in forms characterized by aggressive and metastatic behaviors.Cell Death and Disease (2025) 16:400 ;