2. Academic Validation
  3. Synergistic regulation of DACH1 stability by acetylation and deubiquitination promotes colorectal cancer progression

Synergistic regulation of DACH1 stability by acetylation and deubiquitination promotes colorectal cancer progression

  • Cell Death Dis. 2025 May 19;16(1):400. doi: 10.1038/s41419-025-07696-9.
Liang Zhu # 1,  Can Cheng # 2,  Heng Li 3,  Jingwen Liu 4,  Yang Wu 5,  Liang Wu 6,  Hanhui Yao 7
Affiliations

Affiliations

  • 1 Department of Gastric Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, China.
  • 2 Department of Vascular Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, China.
  • 3 Department of Comprehensive Surgery, Anhui Provincial Cancer Hospital, West District of The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Heifei, China.
  • 4 Health Management Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Heifei, China.
  • 5 Department of Gastric Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, China. po_bid@163.com.
  • 6 Department of Gastric Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, China. wu8722@ustc.edu.cn.
  • 7 Department of Gastric Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, China. yhanhui@ustc.edu.cn.
  • # Contributed equally.
PMID: 40389405 DOI: 10.1038/s41419-025-07696-9
Abstract

Colorectal Cancer (CRC) remains a significant challenge in oncology, with limited therapeutic options for aggressive subtypes. This study elucidates the critical roles of USP7 and DACH1 in CRC, revealing their involvement in tumor progression and potential as therapeutic 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 by removing ubiquitin chains, particularly K48-linked types, which are crucial for protein degradation. Additionally, acetylation at K680 on DACH1, mediated by acetyltransferase GCN5, enhances its interaction with USP7, further influencing DACH1 stability and function. Clinically, high levels of USP7 and DACH1 correlate with poor prognosis in CRC patients, underscoring their significance in disease progression. These findings suggest that targeting the USP7-DACH1 axis could offer a novel therapeutic strategy for managing CRC, particularly in forms characterized by aggressive and metastatic behaviors.

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