{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:55:12Z","timestamp":1791201312485,"version":"4.2.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>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-\u03baB signaling, autophagy, and acquired resistance to chemotherapy or targeted agents. The substrate repertoire of TRIM22 is remarkably broad. It includes p53-related effectors, I-\u03baB\u03b1, NF-\u03baB components, \u03b2-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.<\/jats:p>","DOI":"10.3389\/fcell.2026.1977247","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:09:58Z","timestamp":1791198598000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TRIM22 in cancer: a context-dependent E3 ligase at the interface of interferon, p53, and tumor plasticity"],"prefix":"10.3389","volume":"14","author":[{"given":"Chenjie","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of General Surgery, Changzhou Hospital of Traditional Chinese Medicine","place":["Changzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Urology, Wujin Hospital Affiliated with Jiangsu University","place":["Changzhou, China"]},{"name":"Department of Urology, The Wujin Clinical College of Xuzhou Medical University","place":["Changzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3270","DOI":"10.1158\/0008-5472.can-25-4114","article-title":"Prolonged KRAS-MAPK inhibition induces interferon signaling that promotes cell state transition and confers therapeutic vulnerabilities","volume":"86","author":"Bulle","year":"2026","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.21037\/jgo-22-619","article-title":"Bioinformatics analysis of immune infiltrates and tripartite motif (TRIM) family genes in hepatocellular carcinoma","volume":"13","author":"Cao","year":"2022","journal-title":"J. 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