Work

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

Year: 2025

Type: article

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. Aberrant activation of Wnt/β-catenin signaling contributes to colorectal cancer (CRC) pathogenesis. Here the authors find that the cytoplasmic distribution of TRIM24 E3 ubiquitin ligase triggers ubiquitination and degradation of von Hippel-Lindau, resulting in the accumulation of β-catenin protein in CRC cells.

Source: Nature Communications

DOI: 10.1038/s41467-025-63685-8