Mechanisms and functions of the TRIM protein family in digestive system cancers
- 1Zhejiang Chinese Medical University
- 2Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
Abstract
Background Tripartite motif-containing (TRIM) proteins are important RING-type E3 ubiquitin ligases that regulate protein fate and signal transduction through ubiquitin/ubiquitin-like modifications and non-ubiquitination mechanisms. In digestive system cancers, TRIM proteins exert highly context-dependent bidirectional effects. Here, we conceptualize TRIM proteins as signal integration nodes linking ubiquitin-mediated regulation, core signaling pathways, and adaptation to the tumor microenvironment. Methods This structured narrative review synthesizes English-language studies indexed in PubMed between January 2010 and October 2025. It focuses on the structural basis, multilevel regulation, molecular networks, phenotypic functions, prognostic relevance, and therapeutic implications of TRIM proteins in esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma. Conclusions The modular architecture of TRIM proteins enables diverse substrate recognition and regulatory outputs. Cross-cancer analysis identifies pathway-convergent, phenotype-convergent, and pathway–phenotype bridging TRIM members that translate dysregulation of core pathways, including Wnt/β-catenin, PI3K/AKT, and p53, into proliferative, cell death-related, metastatic, metabolic, and immune phenotypes. Their functional direction is jointly shaped by tumor type, molecular subtype, substrate status, microenvironmental cues, and treatment context. Selected TRIM members show potential as prognostic biomarkers, risk-stratification indicators, and predictors of therapeutic response, whereas most TRIM-targeted strategies remain preclinical. Future studies should clarify ubiquitin-chain-specific regulatory logic, subtype-specific functions, and multilayered networks, while rigorously evaluating the specificity, safety, and clinical applicability of TRIM-directed combination therapies.
Related
- Gut mycobiome dysbiosis in digestive system cancers: immune remodeling and translational implications.
- Protein Lysine Lactylation in DNA Damage Response: Regulatory Mechanisms and Emerging Functions
- Gene functions determine stochastic or adaptive futile transcription in cancers through deregulated start site deployments.
- TRIM28‐Derived Peptide Exerts Anti‐Tumor Roles by Stabilizing Tumor Suppressive BRD7 Protein in Multiple Cancers
- Immunostimulatory functions of membrane-bound and exported heat shock protein 70
BibTeX
@article{xu2026mechanisms,
title = {{Mechanisms and functions of the TRIM protein family in digestive system cancers}},
author = {Yujie Xu and Zhengchen Jiang and Xiangliu Chen and Pengfei Yu},
journal = {Journal of Translational Medicine},
year = {2026},
month = jul,
doi = {10.1186/s12967-026-08661-6},
url = {https://doi.org/10.1186/s12967-026-08661-6},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mechanisms and functions of the TRIM protein family in digestive system cancers
AU - Yujie Xu
AU - Zhengchen Jiang
AU - Xiangliu Chen
AU - Pengfei Yu
PY - 2026
DA - 2026/07/01
JO - Journal of Translational Medicine
DO - 10.1186/s12967-026-08661-6
UR - https://doi.org/10.1186/s12967-026-08661-6
AB - Background Tripartite motif-containing (TRIM) proteins are important RING-type E3 ubiquitin ligases that regulate protein fate and signal transduction through ubiquitin/ubiquitin-like modifications and non-ubiquitination mechanisms. In digestive system cancers, TRIM proteins exert highly context-dependent bidirectional effects. Here, we conceptualize TRIM proteins as signal integration nodes linking ubiquitin-mediated regulation, core signaling pathways, and adaptation to the tumor microenvironment. Methods This structured narrative review synthesizes English-language studies indexed in PubMed between January 2010 and October 2025. It focuses on the structural basis, multilevel regulation, molecular networks, phenotypic functions, prognostic relevance, and therapeutic implications of TRIM proteins in esophageal squamous cell carcinoma, gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma. Conclusions The modular architecture of TRIM proteins enables diverse substrate recognition and regulatory outputs. Cross-cancer analysis identifies pathway-convergent, phenotype-convergent, and pathway–phenotype bridging TRIM members that translate dysregulation of core pathways, including Wnt/β-catenin, PI3K/AKT, and p53, into proliferative, cell death-related, metastatic, metabolic, and immune phenotypes. Their functional direction is jointly shaped by tumor type, molecular subtype, substrate status, microenvironmental cues, and treatment context. Selected TRIM members show potential as prognostic biomarkers, risk-stratification indicators, and predictors of therapeutic response, whereas most TRIM-targeted strategies remain preclinical. Future studies should clarify ubiquitin-chain-specific regulatory logic, subtype-specific functions, and multilayered networks, while rigorously evaluating the specificity, safety, and clinical applicability of TRIM-directed combination therapies.
SN - 1479-5876
ER -