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

Author

Listed:
  • Ya Wang

    (Central South University
    University of South China
    Central South University)

  • Yuanbing Yao

    (Central South University)

  • Zehong Liu

    (Central South University)

  • Shichao Long

    (Central South University)

  • Feng Yi

    (Central South University)

  • Qing Fang

    (University of South China)

  • Dongbo Wu

    (Sichuan University)

  • Qing Zhu

    (Central South University)

  • Hongyan Zai

    (Central South University)

  • Shuai Xiao

    (University of South China
    University of South China
    Hunan Provincial Maternal and Child Health Care Hospital)

  • Fengyi Wan

    (Johns Hopkins University)

  • Kai Fu

    (Central South University
    Central South University
    National Clinical Research Center for Geriatric Disorders
    Central South University)

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.

Suggested Citation

  • Ya Wang & Yuanbing Yao & Zehong Liu & Shichao Long & Feng Yi & Qing Fang & Dongbo Wu & Qing Zhu & Hongyan Zai & Shuai Xiao & Fengyi Wan & Kai Fu, 2025. "Cytoplasmic TRIM24 promotes colorectal cancer cell proliferation by activating Wnt/β-catenin signaling," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63685-8
    DOI: 10.1038/s41467-025-63685-8
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    References listed on IDEAS

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    1. Wen-Wei Tsai & Zhanxin Wang & Teresa T. Yiu & Kadir C. Akdemir & Weiya Xia & Stefan Winter & Cheng-Yu Tsai & Xiaobing Shi & Dirk Schwarzer & William Plunkett & Bruce Aronow & Or Gozani & Wolfgang Fisc, 2010. "TRIM24 links a non-canonical histone signature to breast cancer," Nature, Nature, vol. 468(7326), pages 927-932, December.
    2. Wen Wei & Qiaoli Chen & Minjun Liu & Yang Sheng & Qian OuYang & Weikuan Feng & Xinyu Yang & Longfei Ding & Shu Su & Jingzi Zhang & Lei Fang & Antonio Vidal-Puig & Hong-Yu Wang & Shuai Chen, 2022. "TRIM24 is an insulin-responsive regulator of P-bodies," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Philipp Mertins & D. R. Mani & Kelly V. Ruggles & Michael A. Gillette & Karl R. Clauser & Pei Wang & Xianlong Wang & Jana W. Qiao & Song Cao & Francesca Petralia & Emily Kawaler & Filip Mundt & Karste, 2016. "Proteogenomics connects somatic mutations to signalling in breast cancer," Nature, Nature, vol. 534(7605), pages 55-62, June.
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