2. Academic Validation
  3. Cytoplasmic TRIM24 promotes colorectal cancer cell proliferation by activating Wnt/β-catenin signaling

Cytoplasmic TRIM24 promotes colorectal cancer cell proliferation by activating Wnt/β-catenin signaling

  • Nat Commun. 2025 Sep 29;16(1):8598. doi: 10.1038/s41467-025-63685-8.
Ya Wang # 1 2 3,  Yuanbing Yao # 1,  Zehong Liu 1,  Shichao Long 1,  Feng Yi 1,  Qing Fang 4,  Dongbo Wu 5,  Qing Zhu 6,  Hongyan Zai 6,  Shuai Xiao 7 8 9,  Fengyi Wan 10,  Kai Fu 11 12 13 14
Affiliations

Affiliations

  • 1 Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 2 The First Affiliated Hospital, Hunan Provincial Key Laboratory of Multi-omics and Artificial Intelligence of Cardiovascular Diseases, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
  • 3 MOE Key Lab of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics of the School of Life Sciences, Central South University, Changsha, Hunan, China.
  • 4 The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
  • 5 Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 6 Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 7 The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, China. xiaoshuai1982@hotmail.com.
  • 8 Department of Gastrointestinal Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China. xiaoshuai1982@hotmail.com.
  • 9 National Health Commission Key Laboratory of Birth Defects for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China. xiaoshuai1982@hotmail.com.
  • 10 Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. fwan1@jhu.edu.
  • 11 Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. fu_kai@csu.edu.cn.
  • 12 MOE Key Lab of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics of the School of Life Sciences, Central South University, Changsha, Hunan, China. fu_kai@csu.edu.cn.
  • 13 National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China. fu_kai@csu.edu.cn.
  • 14 Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, Hunan, China. fu_kai@csu.edu.cn.
  • # Contributed equally.
PMID: 41022821 DOI: 10.1038/s41467-025-63685-8
Abstract

Aberrant activation of Wnt/β-catenin signaling is proposed as a major molecular mechanism underlying the occurrence and progression of colorectal Cancer (CRC). However, the precise mechanisms controlling the accumulation of β-catenin protein in CRC cells remain incompletely understood. Here, we show that TRIM24 is elevated in CRC tissues and partially distributed in the cytoplasm. TRIM24 is phosphorylated at serine 1042 by Aurora Kinase B (AURKB), which promotes its cytoplasmic distribution. Subsequently, TRIM24 activates Wnt/β-catenin signaling by facilitating Akt activation through interaction with and ubiquitination of its negative regulator von Hippel-Lindau (VHL), resulting in β-catenin accumulation and enhanced proliferation of CRC cells. Moreover, chemical inhibition of AURKB suppresses tumor growth in subcutaneous mouse model and exhibits particular effectiveness against tumors derived from CRC cells characterized by prominent cytoplasmic TRIM24 distribution. Together, these findings reveal a critical role of TRIM24 in CRC cell proliferation, particularly through activating Wnt/β-catenin signaling.

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