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

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-09-29 DOI:10.1038/s41467-025-63685-8

Ya Wang,Yuanbing Yao,Zehong Liu,Shichao Long,Feng Yi,Qing Fang,Dongbo Wu,Qing Zhu,Hongyan Zai,Shuai Xiao,Fengyi Wan,Kai Fu

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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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细胞质TRIM24通过激活Wnt/β-catenin信号通路促进结直肠癌细胞增殖。

Wnt/β-catenin信号的异常激活被认为是结直肠癌（CRC）发生和发展的主要分子机制。然而，控制结直肠癌细胞中β-catenin蛋白积累的确切机制仍不完全清楚。在这里，我们发现TRIM24在结直肠癌组织中升高，部分分布在细胞质中。TRIM24在丝氨酸1042位点被极光激酶B （AURKB）磷酸化，从而促进其细胞质分布。随后，TRIM24通过与负调节因子von Hippel-Lindau （VHL）相互作用和泛素化，促进AKT活化，从而激活Wnt/β-catenin信号通路，导致β-catenin积累，增强CRC细胞的增殖。此外，AURKB的化学抑制抑制了皮下小鼠模型中的肿瘤生长，并对以胞质显著分布的TRIM24为特征的CRC细胞衍生的肿瘤表现出特别的有效性。总之，这些发现揭示了TRIM24在结直肠癌细胞增殖中的关键作用，特别是通过激活Wnt/β-catenin信号传导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.