TRIM22 in cancer: a context-dependent E3 ligase at the interface of interferon, p53, and tumor plasticity.
- 1Department of General Surgery, Changzhou Hospital of Traditional Chinese Medicine, Changzhou, China.
- 2Department of Urology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, China.
- 3Department of Urology, The Wujin Clinical College of Xuzhou Medical University, Changzhou, China.
Abstract
TRIM22 is a TRIM family E3 ubiquitin ligase whose expression is strongly induced by interferons. For many years, it has been identified primarily as an antiviral effector, a role that remains well validated. A growing body of cancer-related work now forces us to expand that view considerably. Depending on tumor type, upstream signaling context, and the specific substrates available in a given cell, TRIM22 can either constrain malignancy or actively promote it. In breast, colorectal, ovarian, endometrial, hepatocellular, cervical, and gastric cancers, as well as in certain lung tumor subsets, TRIM22 is frequently downregulated or functionally impaired. Where this occurs, its re-expression tends to curb proliferation, invasion, stemness, and cachexia-associated programs. Conversely, in non-small-cell lung carcinoma, glioblastoma, melanoma, and pancreatic ductal adenocarcinoma, TRIM22 often takes on a pro-tumorigenic role. It drives epithelial mesenchymal transition, NF-κB signaling, autophagy, and acquired resistance to chemotherapy or targeted agents. The substrate repertoire of TRIM22 is remarkably broad. It includes p53-related effectors, I-κBα, NF-κB components, β-catenin, TCF4, CCS-STAT3, PHLPP2, Raf-1, p21, ADRB2, CDT2, and Smad2. In this review, we synthesize recent findings and argue that TRIM22 functions as a stress-responsive ubiquitin signaling hub rather than as a conventional oncogene or tumor suppressor. It integrates inputs from interferons, p53, hormonal cues, and inflammatory pathways. The phenotypic outcome, whether tumor suppression or tumor promotion, is dictated by cellular lineage and the pre-existing molecular wiring. Deciphering this contextual logic is the key to translating TRIM22 biology into clinically useful strategies.
Related
- The Context-Dependent Regulation and Function of Notch Signaling as a Molecular Mediator of Tumor Plasticity
- VIRMA-associated SRD5A2 downregulation promotes BPH progression through ERα-CREB5-dependent epithelial plasticity
- NEU3 at the Plasma Membrane: Context-Dependent Ganglioside Remodeling in Health and Disease
- Multiple copies of the Mason-Pfizer monkey virus constitutive RNA transport element lead to enhanced HIV-1 Gag expression in a context-dependent manner
- Bisphenol A and prostate cancer: from population exposure to context-dependent mechanisms and translational implications
BibTeX
@article{qiu2026trim22,
title = {{TRIM22 in cancer: a context-dependent E3 ligase at the interface of interferon, p53, and tumor plasticity.}},
author = {Chenjie Qiu and Liangliang Dai},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1977247},
url = {https://europepmc.org/article/MED/42898983},
note = {CC BY},
}
RIS
TY - JOUR
TI - TRIM22 in cancer: a context-dependent E3 ligase at the interface of interferon, p53, and tumor plasticity.
AU - Chenjie Qiu
AU - Liangliang Dai
PY - 2026
DA - 2026/10/05
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1977247
UR - https://europepmc.org/article/MED/42898983
AB - TRIM22 is a TRIM family E3 ubiquitin ligase whose expression is strongly induced by interferons. For many years, it has been identified primarily as an antiviral effector, a role that remains well validated. A growing body of cancer-related work now forces us to expand that view considerably. Depending on tumor type, upstream signaling context, and the specific substrates available in a given cell, TRIM22 can either constrain malignancy or actively promote it. In breast, colorectal, ovarian, endometrial, hepatocellular, cervical, and gastric cancers, as well as in certain lung tumor subsets, TRIM22 is frequently downregulated or functionally impaired. Where this occurs, its re-expression tends to curb proliferation, invasion, stemness, and cachexia-associated programs. Conversely, in non-small-cell lung carcinoma, glioblastoma, melanoma, and pancreatic ductal adenocarcinoma, TRIM22 often takes on a pro-tumorigenic role. It drives epithelial mesenchymal transition, NF-κB signaling, autophagy, and acquired resistance to chemotherapy or targeted agents. The substrate repertoire of TRIM22 is remarkably broad. It includes p53-related effectors, I-κBα, NF-κB components, β-catenin, TCF4, CCS-STAT3, PHLPP2, Raf-1, p21, ADRB2, CDT2, and Smad2. In this review, we synthesize recent findings and argue that TRIM22 functions as a stress-responsive ubiquitin signaling hub rather than as a conventional oncogene or tumor suppressor. It integrates inputs from interferons, p53, hormonal cues, and inflammatory pathways. The phenotypic outcome, whether tumor suppression or tumor promotion, is dictated by cellular lineage and the pre-existing molecular wiring. Deciphering this contextual logic is the key to translating TRIM22 biology into clinically useful strategies.
SN - 2296-634X
ER -