{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:48:40Z","timestamp":1792097320821,"version":"4.4.0"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":256,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Institutes of Health National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA271537"],"award-info":[{"award-number":["R01CA271537"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA207913"],"award-info":[{"award-number":["R01CA207913"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA046934"],"award-info":[{"award-number":["P30CA046934"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX004935-01"],"award-info":[{"award-number":["BX004935-01"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010174","name":"University of Colorado","doi-asserted-by":"publisher","award":["P30CA046934"],"award-info":[{"award-number":["P30CA046934"]}],"id":[{"id":"10.13039\/100010174","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Letters"],"published-print":{"date-parts":[[2026,2]]},"DOI":"10.1016\/j.canlet.2025.218172","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:50:34Z","timestamp":1764291034000},"page":"218172","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Melanoma leverages innate immune IRAK-M signaling to limit metastasis through PTPN22-Induced signaling repression"],"prefix":"10.1016","volume":"639","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3558-0194","authenticated-orcid":false,"given":"Degui","family":"Geng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangli","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian Andres","family":"Davalos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pearl","family":"Wilcox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Gonzales-Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2088-2229","authenticated-orcid":false,"given":"Kasey","family":"Couts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Tobin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5881-3184","authenticated-orcid":false,"given":"Allison Joy","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"McCarter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsey","family":"Crump","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Tsujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Breelyn Ann","family":"Wilky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9738-4167","authenticated-orcid":false,"given":"Eduardo","family":"Davila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.canlet.2025.218172_bib1","doi-asserted-by":"crossref","DOI":"10.7717\/peerj.3754","article-title":"Quantitative comparison of the spreading and invasion of radial growth phase and metastatic melanoma cells in a three-dimensional human skin equivalent model","volume":"5","author":"Haridas","year":"2017","journal-title":"PeerJ"},{"key":"10.1016\/j.canlet.2025.218172_bib2","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1001\/jamadermatol.2022.0160","article-title":"Global Burden of Cutaneous Melanoma in 2020 and Projections to 2040","volume":"158","author":"Arnold","year":"2022","journal-title":"JAMA Dermatol."},{"key":"10.1016\/j.canlet.2025.218172_bib3","doi-asserted-by":"crossref","first-page":"553","DOI":"10.3389\/fimmu.2014.00553","article-title":"IL-1 receptor-associated kinase signaling and its role in inflammation, cancer progression, and therapy resistance","volume":"5","author":"Jain","year":"2014","journal-title":"Front. Immunol."},{"issue":"3","key":"10.1016\/j.canlet.2025.218172_bib4","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1172\/JCI75821","article-title":"Inhibition of IRAK1\/4 sensitizes T cell acute lymphoblastic leukemia to chemotherapies","volume":"125","author":"Li","year":"2015","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.canlet.2025.218172_bib5","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.ccr.2013.05.006","article-title":"Targeting IRAK1 as a therapeutic approach for myelodysplastic syndrome","volume":"24","author":"Rhyasen","year":"2013","journal-title":"Cancer Cell"},{"key":"10.1016\/j.canlet.2025.218172_bib6","doi-asserted-by":"crossref","first-page":"6209","DOI":"10.1158\/0008-5472.CAN-12-0337","article-title":"Augmentation of therapeutic responses in melanoma by inhibition of IRAK-1,-4","volume":"72","author":"Srivastava","year":"2012","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2025.218172_bib7","first-page":"13","article-title":"Interleukin-1 receptor-associated kinase 1 in cancer metastasis and therapeutic resistance: mechanistic insights and translational advances","author":"Najjar","year":"2024","journal-title":"Cells"},{"key":"10.1016\/j.canlet.2025.218172_bib8","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/s42003-020-1033-y","article-title":"Induction of IRAK-M in melanoma induces caspase-3 dependent apoptosis by reducing TRAF6 and calpastatin levels","volume":"3","author":"Geng","year":"2020","journal-title":"Commun. Biol."},{"key":"10.1016\/j.canlet.2025.218172_bib9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/s41419-023-05621-6","article-title":"IRAK-M suppresses the activation of microglial NLRP3 inflammasome and GSDMD-mediated pyroptosis through inhibiting IRAK1 phosphorylation during experimental autoimmune encephalomyelitis","volume":"14","author":"Wang","year":"2023","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.canlet.2025.218172_bib10","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0092-8674(02)00827-9","article-title":"IRAK-M is a negative regulator of toll-like receptor signaling","volume":"110","author":"Kobayashi","year":"2002","journal-title":"Cell"},{"key":"10.1016\/j.canlet.2025.218172_bib11","doi-asserted-by":"crossref","first-page":"19403","DOI":"10.1074\/jbc.274.27.19403","article-title":"IRAK-M is a novel member of the Pelle\/interleukin-1 receptor-associated kinase (IRAK) family","volume":"274","author":"Wesche","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2025.218172_bib12","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1146\/annurev-immunol-032713-120249","article-title":"Tyrosine phosphatase PTPN22: multifunctional regulator of immune signaling, development, and disease","volume":"32","author":"Bottini","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.canlet.2025.218172_bib13","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.aaw8130","article-title":"PTPN22 phosphorylation acts as a molecular rheostat for the inhibition of TCR signaling","volume":"13","author":"Yang","year":"2020","journal-title":"Sci. Signal."},{"key":"10.1016\/j.canlet.2025.218172_bib14","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/10985549.2024.2378810","article-title":"Regulation of T cell signaling and immune responses by PTPN22","volume":"44","author":"Brownlie","year":"2024","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.canlet.2025.218172_bib15","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1111\/febs.16021","article-title":"Epithelial-to-mesenchymal-like transition events in melanoma","volume":"289","author":"Pedri","year":"2022","journal-title":"FEBS J."},{"key":"10.1016\/j.canlet.2025.218172_bib16","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41586-019-1689-y","article-title":"Pan-cancer whole-genome analyses of metastatic solid tumours","volume":"575","author":"Priestley","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.canlet.2025.218172_bib17","first-page":"12","article-title":"EMT-Inducing transcription factors, drivers of Melanoma phenotype switching, and resistance to treatment","author":"Tang","year":"2020","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.canlet.2025.218172_bib18","doi-asserted-by":"crossref","first-page":"6382","DOI":"10.1158\/0008-5472.CAN-12-1033","article-title":"TWIST1 is an ERK1\/2 effector that promotes invasion and regulates MMP-1 expression in human melanoma cells","volume":"72","author":"Weiss","year":"2012","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2025.218172_bib19","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1038\/ng1634","article-title":"The melanocyte differentiation program predisposes to metastasis after neoplastic transformation","volume":"37","author":"Gupta","year":"2005","journal-title":"Nat. Genet."},{"key":"10.1016\/j.canlet.2025.218172_bib20","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1038\/s41467-020-16066-2","article-title":"Context specificity of the EMT transcriptional response","volume":"11","author":"Cook","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.canlet.2025.218172_bib21","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1038\/sj.onc.1205298","article-title":"Src kinase contributes to the metastatic spread of carcinoma cells","volume":"21","author":"Boyer","year":"2002","journal-title":"Oncogene"},{"key":"10.1016\/j.canlet.2025.218172_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2022.110389","article-title":"Activity of ROCKII not ROCKI promotes pulmonary metastasis of melanoma cells via modulating Smad2\/3-MMP9 and FAK-Src-VEGF signalling","volume":"97","author":"Chatterjee","year":"2022","journal-title":"Cell. Signal."},{"key":"10.1016\/j.canlet.2025.218172_bib23","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/sj.bjc.6690763","article-title":"Matrix metalloproteinases in human melanoma cell lines and xenografts: increased expression of activated matrix metalloproteinase-2 (MMP-2) correlates with melanoma progression","volume":"81","author":"Hofmann","year":"1999","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.canlet.2025.218172_bib24","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/CMR.0b013e328304974c","article-title":"Src activation in melanoma and src inhibitors as therapeutic agents in melanoma","volume":"19","author":"Homsi","year":"2009","journal-title":"Melanoma Res."},{"key":"10.1016\/j.canlet.2025.218172_bib25","doi-asserted-by":"crossref","first-page":"6062","DOI":"10.1038\/ncomms7062","article-title":"Glucocorticoids suppress inflammation via the upregulation of negative regulator IRAK-M","volume":"6","author":"Miyata","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.canlet.2025.218172_bib26","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/emboj.2013.2","article-title":"IRAK-M mediates toll-like receptor\/IL-1R-induced NFkappaB activation and cytokine production","volume":"32","author":"Zhou","year":"2013","journal-title":"EMBO J."},{"key":"10.1016\/j.canlet.2025.218172_bib27","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.4049\/jimmunol.1600009","article-title":"Epigenetic and transcriptional regulation of IRAK-M expression in macrophages","volume":"198","author":"Lyroni","year":"2017","journal-title":"J. Immunol."},{"key":"10.1016\/j.canlet.2025.218172_bib28","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1133354","article-title":"Regulation of innate immune signaling by IRAK proteins","volume":"14","author":"Pereira","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.canlet.2025.218172_bib29","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12931-023-02406-5","article-title":"IRAK-M has effects in regulation of lung epithelial inflammation","volume":"24","author":"Li","year":"2023","journal-title":"Respir. Res."},{"key":"10.1016\/j.canlet.2025.218172_bib30","doi-asserted-by":"crossref","first-page":"4758","DOI":"10.1172\/JCI59492","article-title":"T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice","volume":"121","author":"Wiede","year":"2011","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.canlet.2025.218172_bib31","doi-asserted-by":"crossref","DOI":"10.1172\/JCI146950","article-title":"Systemic inhibition of PTPN22 augments anticancer immunity","volume":"131","author":"Ho","year":"2021","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.canlet.2025.218172_bib32","doi-asserted-by":"crossref","first-page":"23173","DOI":"10.1074\/jbc.M101219200","article-title":"Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase","volume":"276","author":"Chiang","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.canlet.2025.218172_bib33","doi-asserted-by":"crossref","first-page":"ra99","DOI":"10.1126\/scisignal.aaf2195","article-title":"Superresolution imaging of the cytoplasmic phosphatase PTPN22 links integrin-mediated T cell adhesion with autoimmunity","volume":"9","author":"Burn","year":"2016","journal-title":"Sci. Signal."},{"key":"10.1016\/j.canlet.2025.218172_bib34","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nrc1366","article-title":"A renaissance for SRC","volume":"4","author":"Yeatman","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.canlet.2025.218172_bib35","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1158\/1535-7163.MCT-09-0151","article-title":"Effects of Src kinase inhibition induced by dasatinib in non-small cell lung cancer cell lines treated with cisplatin","volume":"8","author":"Ceppi","year":"2009","journal-title":"Mol. Cancer Therapeut."},{"key":"10.1016\/j.canlet.2025.218172_bib36","doi-asserted-by":"crossref","first-page":"5706","DOI":"10.1158\/1078-0432.CCR-15-2845","article-title":"TBCRC-010: phase I\/II study of dasatinib in combination with zoledronic acid for the treatment of breast cancer bone metastasis","volume":"22","author":"Mitri","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.canlet.2025.218172_bib37","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/bjc.2011.514","article-title":"Phase I clinical trial of the Src inhibitor dasatinib with dacarbazine in metastatic melanoma","volume":"106","author":"Algazi","year":"2012","journal-title":"Br. J. Cancer"}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030438352500744X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030438352500744X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:39:38Z","timestamp":1792096778000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S030438352500744X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":37,"alternative-id":["S030438352500744X"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2025.218172","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Melanoma leverages innate immune IRAK-M signaling to limit metastasis through PTPN22-Induced signaling repression","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2025.218172","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"218172"}}