2. Academic Validation
  3. CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer

CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer

  • Acta Pharm Sin B. 2025 Apr;15(4):1938-1955. doi: 10.1016/j.apsb.2025.02.014.
Liang Wu 1,  Can Cheng 2,  Ning Zhao 3,  Liang Zhu 1,  Heng Li 4,  Jingwen Liu 5,  Yang Wu 1,  Xi Chen 1,  Hanhui Yao 1,  Lianxin Liu 6
Affiliations

Affiliations

  • 1 Department of Gastrointestinal 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 230001, 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 230001, China.
  • 3 Department of Surgical Oncology, the First Affiliated Hospital of Xi'an JiaoTong University, Xi'an 710061, China.
  • 4 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, Hefei 230001, China.
  • 5 Health Management Center, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Heifei 230001, China.
  • 6 Department of Hepatobiliary 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, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China.
PMID: 40486858 DOI: 10.1016/j.apsb.2025.02.014
Abstract

Colorectal Cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide Deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its Deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

Keywords

CDK1; Colorectal cancer; Dacarbazine; Deubiquitination; Oncogenesis; Phosphorylation; SND1; USP37.

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