{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:25:12Z","timestamp":1787297112533,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82303655"],"award-info":[{"award-number":["82303655"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403698"],"award-info":[{"award-number":["82403698"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2024NSCQ\u2010MSX1163"],"award-info":[{"award-number":["CSTB2024NSCQ\u2010MSX1163"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tripartite motif\u2010containing 59 (TRIM59) is an E3 ubiquitin ligase implicated in multiple malignancies, but its role in bladder cancer (BLCA) remains incompletely understood. In this study, we identified TRIM59 as a clinically relevant oncogenic driver in BLCA through integrated transcriptomic, clinical, and functional analyses. TRIM59 was significantly upregulated in BLCA tissues and cell lines, and high TRIM59 expression was associated with advanced stage, higher grade, recurrence, and poor prognosis. Functionally, TRIM59 promoted BLCA proliferation, cell\u2010cycle progression, migration, invasion, and metastatic colonization in\u00a0vitro and in\u00a0vivo. Mechanistically, TRIM59 directly interacted with PTRF\/Cavin\u20101 and induced its RING domain\u2010dependent K48\u2010linked polyubiquitination and proteasomal degradation. Additional mutagenesis analyses identified K98, K122, K152, and K317 as major ubiquitination sites on PTRF. In contrast to the oncogenic role of TRIM59, PTRF was downregulated in BLCA and exhibited tumor\u2010suppressive properties. PTRF restoration attenuated TRIM59\u2010driven proliferation, invasion, and epithelial\u2010mesenchymal transition, whereas PTRF depletion partially rescued the inhibitory effects of TRIM59 silencing. Further analyses showed that PTRF restrains AKT phosphorylation and suppresses MYC transcriptional activity, thereby limiting c\u2010Myc\u2010driven proliferative signaling. Collectively, these findings define a previously unrecognized TRIM59\u2013PTRF\u2013AKT\/c\u2010Myc axis that drives BLCA progression and highlight TRIM59 as a potential prognostic biomarker and therapeutic target.<\/jats:p>","DOI":"10.1111\/cas.70510","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:02:56Z","timestamp":1787295776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TRIM59<\/scp>\n                    Drives Bladder Cancer Progression Through\n                    <scp>E3<\/scp>\n                    Ligase\u2010Dependent\n                    <scp>K48<\/scp>\n                    \u2010Linked Degradation of\n                    <scp>PTRF<\/scp>"],"prefix":"10.1111","author":[{"given":"Junlin","family":"Gan","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Basic Laboratory Suining Central Hospital  Suining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Urology, Urology Research Institute The First Affiliated Hospital of Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6583-3017","authenticated-orcid":false,"given":"Hang","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinghao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7909-7025","authenticated-orcid":false,"given":"Ning","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology, Urology Research Institute The First Affiliated Hospital of Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urology Suining Central Hospital  Suining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3972-9016","authenticated-orcid":false,"given":"Hubin","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Department of Urology, Urology Research Institute The First Affiliated Hospital of Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"issue":"3","key":"e_1_2_19_2_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray F.","year":"2024","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"1","key":"e_1_2_19_3_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41572-023-00468-9","article-title":"Bladder Cancer","volume":"9","author":"Dyrskj\u00f8t L.","year":"2023","journal-title":"Nature Reviews Disease Primers"},{"issue":"5","key":"e_1_2_19_4_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells8050510","article-title":"E3 Ubiquitin Ligase TRIM Proteins, Cell Cycle and Mitosis","volume":"8","author":"Venuto S.","year":"2019","journal-title":"Cells"},{"issue":"1","key":"e_1_2_19_5_1","doi-asserted-by":"crossref","DOI":"10.1186\/s40164-022-00322-w","article-title":"TRIM Family Contribute to Tumorigenesis, Cancer Development, and Drug Resistance","volume":"11","author":"Huang N.","year":"2022","journal-title":"Experimental Hematology & Oncology"},{"issue":"24","key":"e_1_2_19_6_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells13242107","article-title":"The Role and Mechanism of TRIM Proteins in Gastric Cancer","volume":"13","author":"Wu W.","year":"2024","journal-title":"Cells"},{"issue":"1","key":"e_1_2_19_7_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s12079-017-0423-5","article-title":"TRIM Proteins in Blood Cancers","volume":"12","author":"Crawford L. J.","year":"2018","journal-title":"Journal of Cell Communication and Signaling"},{"issue":"1","key":"e_1_2_19_8_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-025-07913-5","article-title":"TRIM59 Suppresses Mitochondrial\u2010Associated Apoptosis to Facilitate Progression in Papillary Renal Cell Carcinoma via the ACAT1\u2010Cardiolipin Pathway","volume":"16","author":"Weng H.","year":"2025","journal-title":"Cell Death & Disease"},{"issue":"12","key":"e_1_2_19_9_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-024-07324-y","article-title":"TRIM59\/RBPJ Positive Feedback Circuit Confers Gemcitabine Resistance in Pancreatic Cancer by Activating the Notch Signaling Pathway","volume":"15","author":"Chen S.","year":"2024","journal-title":"Cell Death & Disease"},{"issue":"8","key":"e_1_2_19_10_1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41388-022-02498-1","article-title":"TRIM59 Is Suppressed by Androgen Receptor and Acts to Promote Lineage Plasticity and Treatment\u2010Induced Neuroendocrine Differentiation in Prostate Cancer","volume":"42","author":"Fan L.","year":"2023","journal-title":"Oncogene"},{"issue":"14","key":"e_1_2_19_11_1","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.7150\/ijbs.28757","article-title":"TRIM59 Is a Novel Marker of Poor Prognosis and Promotes Malignant Progression of Ovarian Cancer by Inducing Annexin A2 Expression","volume":"14","author":"Wang Y.","year":"2018","journal-title":"International Journal of Biological Sciences"},{"key":"e_1_2_19_12_1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.canlet.2019.12.030","article-title":"TRIM59 Promotes Tumor Growth in Hepatocellular Carcinoma and Regulates the Cell Cycle by Degradation of Protein Phosphatase 1B","volume":"473","author":"Ying H.","year":"2020","journal-title":"Cancer Letters"},{"issue":"9","key":"e_1_2_19_13_1","doi-asserted-by":"crossref","DOI":"10.31083\/FBL44395","article-title":"Identification of TRIM59 as a Key Biomarker for Ferroptosis Resistance and Immunotherapy Response in Bladder Cancer via Multi\u2010Omics Integration and Machine Learning","volume":"30","author":"Lei J.","year":"2025","journal-title":"Front Biosci (Landmark Ed)"},{"issue":"3","key":"e_1_2_19_14_1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1111\/cas.70286","article-title":"KAT2A Deficiency Suppresses Lung Cancer Progression by Downregulating MYC Through Decreasing MYC Succinylation","volume":"117","author":"Li J.","year":"2026","journal-title":"Cancer Science"},{"key":"e_1_2_19_15_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.218146","article-title":"Transglutaminase 2 Facilitates Metastasis of Basal\u2010Like Bladder Cancer by Sustaining MVP\u2010Mediated MAPK\/ERK1\/2 Signaling Activation","volume":"636","author":"Chen D.","year":"2026","journal-title":"Cancer Letters"},{"key":"e_1_2_19_16_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.canlet.2016.11.020","article-title":"DNA Methylation Profiling Identifies PTRF\/Cavin\u20101 as a Novel Tumor Suppressor in Ewing Sarcoma When Co\u2010Expressed With Caveolin\u20101","volume":"386","author":"Huertas\u2010Mart nez J.","year":"2017","journal-title":"Cancer Letters"},{"issue":"9","key":"e_1_2_19_17_1","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.7150\/thno.71763","article-title":"PTRF\/Cavin\u20101 Enhances Chemo\u2010Resistance and Promotes Temozolomide Efflux Through Extracellular Vesicles in Glioblastoma","volume":"12","author":"Yang E.","year":"2022","journal-title":"Theranostics"},{"issue":"2","key":"e_1_2_19_18_1","doi-asserted-by":"crossref","DOI":"10.1093\/bib\/bbab574","article-title":"GPS\u2010Uber: A Hybrid\u2010Learning Framework for Prediction of General and E3\u2010Specific Lysine Ubiquitination Sites","volume":"23","author":"Wang C.","year":"2022","journal-title":"Briefings in Bioinformatics"},{"issue":"11","key":"e_1_2_19_19_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2025.110734","article-title":"Loss of TRIM44 Promotes Renal Cell Carcinoma Progression by Regulating K48\u2010Linked Ubiquitination of Vimentin","volume":"301","author":"Ke S.","year":"2025","journal-title":"Journal of Biological Chemistry"},{"issue":"1","key":"e_1_2_19_20_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13046-019-1138-7","article-title":"TRIM44 Activates the AKT\/mTOR Signal Pathway to Induce Melanoma Progression by Stabilizing TLR4","volume":"38","author":"Wei C.","year":"2019","journal-title":"Journal of Experimental & Clinical Cancer Research"},{"issue":"1","key":"e_1_2_19_21_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-025-08074-1","article-title":"The E3 Ubiquitin Ligase TRIM56 Promotes Aggregation and Activation of Src Protein Through Lys63\u2010Linked Polyubiquitination in Hepatocellular Carcinoma","volume":"16","author":"Zhu L.","year":"2025","journal-title":"Cell Death & Disease"},{"issue":"3","key":"e_1_2_19_22_1","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1002\/jcp.26114","article-title":"The Ubiquitin Ligase TRIM56 Inhibits Ovarian Cancer Progression by Targeting Vimentin","volume":"233","author":"Zhao L.","year":"2018","journal-title":"Journal of Cellular Physiology"},{"issue":"44","key":"e_1_2_19_23_1","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1038\/s41388-023-02843-y","article-title":"SLC35F2\u2010SYVN1\u2010TRIM59 Axis Critically Regulates Ferroptosis of Pancreatic Cancer Cells by Inhibiting Endogenous p53","volume":"42","author":"Ben C.","year":"2023","journal-title":"Oncogene"},{"issue":"5","key":"e_1_2_19_24_1","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1053\/j.gastro.2014.07.021","article-title":"TRIM59 Is Up\u2010Regulated in Gastric Tumors, Promoting Ubiquitination and Degradation of p53","volume":"147","author":"Zhou Z.","year":"2014","journal-title":"Gastroenterology"},{"issue":"1","key":"e_1_2_19_25_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-12001-2","article-title":"CDK5\u2010Dependent Phosphorylation and Nuclear Translocation of TRIM59 Promotes macroH2A1 Ubiquitination and Tumorigenicity","volume":"10","author":"Sang Y.","year":"2019","journal-title":"Nature Communications"},{"issue":"9","key":"e_1_2_19_26_1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nrurol.2013.168","article-title":"Caveola\u2010Forming Proteins Caveolin\u20101 and PTRF in Prostate Cancer","volume":"10","author":"Nassar Z. D.","year":"2013","journal-title":"Nature Reviews Urology"},{"issue":"3","key":"e_1_2_19_27_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/neuonc\/noaa255","article-title":"PTRF\/Cavin\u20101 Remodels Phospholipid Metabolism to Promote Tumor Proliferation and Suppress Immune Responses in Glioblastoma by Stabilizing cPLA2","volume":"23","author":"Yi K.","year":"2021","journal-title":"Neuro\u2010Oncology"},{"key":"e_1_2_19_28_1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/neuonc\/noaf253","article-title":"PEAKS Activation by PROTAC EPIC\u20100726 Potentiates Temozolomide in Glioblastoma via K63\/K48 Ubiquitination\u2010Dependent ERK\/AKT Suppression and p21 Stabilization","volume":"28","author":"Hong B.","year":"2025","journal-title":"Neuro\u2010Oncology"},{"issue":"1","key":"e_1_2_19_29_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13046-025-03573-7","article-title":"Targeting TRIM59 Impairs RNA Splicing and Promotes Neuroblastoma Differentiation and Therapeutic Responses","volume":"45","author":"Zhang Y.","year":"2025","journal-title":"Journal of Experimental & Clinical Cancer Research"},{"issue":"1","key":"e_1_2_19_30_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41419-025-07932-2","article-title":"Degradation of IRF6 by TRIM59 in Tumor Cells Triggers PGM1\u2010Mediated Glycolysis to Regulate Cell Proliferation in Neuroblastoma","volume":"16","author":"Zeng L.","year":"2025","journal-title":"Cell Death & Disease"},{"issue":"11","key":"e_1_2_19_31_1","doi-asserted-by":"crossref","first-page":"8236","DOI":"10.1002\/jcp.29478","article-title":"TRIM59, Amplified in Ovarian Cancer, Promotes Tumorigenesis Through the MKP3\/ERK Pathway","volume":"235","author":"Tong X.","year":"2020","journal-title":"Journal of Cellular Physiology"},{"issue":"2","key":"e_1_2_19_32_1","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1002\/jcb.29433","article-title":"TRIM59 Predicts Poor Prognosis and Promotes Pancreatic Cancer Progression via the PI3K\/AKT\/mTOR\u2010Glycolysis Signaling Axis","volume":"121","author":"Li R.","year":"2020","journal-title":"Journal of Cellular Biochemistry"},{"issue":"11","key":"e_1_2_19_33_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3000051","article-title":"TRIM59 Promotes Breast Cancer Motility by Suppressing p62\u2010Selective Autophagic Degradation of PDCD10","volume":"16","author":"Tan P.","year":"2018","journal-title":"PLoS Biology"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70510","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70510","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70510","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T07:03:01Z","timestamp":1787295781000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":32,"alternative-id":["10.1111\/cas.70510"],"URL":"https:\/\/doi.org\/10.1111\/cas.70510","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"assertion":[{"value":"2026-02-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cas.70510"}}