Work

TRIM24 promotes proliferation and metastasis of gastric cancer via mediating NRBP1 ubiquitination

Year: 2025

Type: article

Abstract: The early detection and precise treatment of gastric cancer (GC) remain critical challenges worldwide. In this work, we screened and identified a subset of highly aggressive GC cell lines that exhibit elevated expression of TRIM24 using transwell assays and animal models. TRIM24 showed enhanced expression in GC cells and gastric carcinoma tissue samples in comparison with gastric noncancerous tissues. Importantly, elevated TRIM24 levels correlated with advanced tumor stage and poorer clinical outcomes. Functionally, TRIM24 acted as an oncogene, driving GC proliferation, invasion, and metastasis both in cell culture and animal experiments. Notably, TRIM24 knockdown markedly inducted apoptosis in GC cells through the modulation of NRBP1, a known context-specific tumor suppressor. Mechanistically, TRIM24 bound to NRBP1, enhancing its ubiquitination and subsequent degradation. Further mechanistic insights revealed that NRBP1 phosphorylation at residue S42 was crucial for TRIM24-mediated ubiquitination, with residue K430 identified as the specific ubiquitination site targeted by TRIM24. Jointly, the above findings unveil a critical role for TRIM24 in GC tumorigenesis and metastatic progression, thereby positioning TRIM24 as a promising therapeutic target in GC management.

Source: Cell Death and Disease

DOI: 10.1038/s41419-025-08346-w