{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:43:43Z","timestamp":1792554223182,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["82470590"],"award-info":[{"award-number":["82470590"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012269","name":"Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province","doi-asserted-by":"publisher","award":["2023\u2010233"],"award-info":[{"award-number":["2023\u2010233"]}],"id":[{"id":"10.13039\/501100012269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>NIMA\u2010related kinase 2 (NEK2) is a cell cycle regulator aberrantly overexpressed in multiple cancers, yet its non\u2010mitotic roles in oral squamous cell carcinoma (OSCC) invasion and metastasis remain unclear. Here, we analyzed public transcriptomic and single\u2010cell datasets and found that NEK2 is significantly upregulated in OSCC tissues, with higher expression in cases exhibiting lymph node metastasis and associations with poor prognosis. Functional assays demonstrated that NEK2 promotes OSCC cell proliferation, migration, invasion, and epithelial\u2013mesenchymal transition (EMT). Transcriptomic and pathway analyses revealed that NEK2 activates TNF\u2010\u03b1 inflammatory signaling, and rescue experiments confirmed that the pro\u2010invasive effects of NEK2 are largely dependent on TNF\u2010\u03b1 pathway activation. Through immunoprecipitation\u2013mass spectrometry, we identified three core desmosomal proteins\u2014desmoplakin (DSP), desmoglein\u20101 (DSG1), and junction plakoglobin (JUP)\u2014as novel NEK2\u2010interacting partners. NEK2 binding impaired desmosomal adhesion function at cell\u2013cell junctions, and DSP overexpression partially rescued NEK2\u2010induced TNF\u2010\u03b1 secretion, EMT, and invasion. In\u00a0vivo, NEK2 knockdown suppressed xenograft tumor growth, preserved junctional desmosomal protein localization, and downregulated TNF\u2010\u03b1 target genes. Collectively, our findings uncover a NEK2\u2013desmosome\u2013TNF\u2010\u03b1 signaling axis that drives OSCC invasion and metastasis, providing new mechanistic insights and highlighting NEK2 as a potential therapeutic target.<\/jats:p>","DOI":"10.1002\/biof.70161","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:31:48Z","timestamp":1792553508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>NEK2<\/scp>\n                    Promotes\n                    <scp>OSCC<\/scp>\n                    Invasion and Metastasis by Activating\n                    <scp>TNF<\/scp>\n                    \u2010\u03b1 Signaling Through Impairment of Desmosomal Adhesion"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5616-2826","authenticated-orcid":false,"given":"Ziyi","family":"Yan","sequence":"first","affiliation":[{"name":"Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Hunan Province Key Laboratory of Tumor Cellular &amp; Molecular Pathology, Cancer Research Institute Hengyang Medical School, University of South China  Hengyang Hunan China"},{"name":"Stomatology Medical Center The Second Affiliated Hospital, University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuangzheng","family":"Li","sequence":"additional","affiliation":[{"name":"Stomatology Medical Center The Second Affiliated Hospital, University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xia","sequence":"additional","affiliation":[{"name":"Stomatology Medical Center The Second Affiliated Hospital, University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Qian","sequence":"additional","affiliation":[{"name":"Stomatology Medical Center The Second Affiliated Hospital, University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3842-0317","authenticated-orcid":false,"given":"Youxiang","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Hunan Province Key Laboratory of Tumor Cellular &amp; Molecular Pathology, Cancer Research Institute Hengyang Medical School, University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-539X","authenticated-orcid":false,"given":"Deliang","family":"Cao","sequence":"additional","affiliation":[{"name":"Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Hunan Province Key Laboratory of Tumor Cellular &amp; Molecular Pathology, Cancer Research Institute Hengyang Medical School, University of South China  Hengyang Hunan China"},{"name":"Stomatology Medical Center The Second Affiliated Hospital, University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2411-5377","authenticated-orcid":false,"given":"Jiliang","family":"Xia","sequence":"additional","affiliation":[{"name":"Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Hunan Province Key Laboratory of Tumor Cellular &amp; Molecular Pathology, Cancer Research Institute Hengyang Medical School, University of South China  Hengyang Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"issue":"1","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and Neck Squamous Cell Carcinoma","volume":"6","author":"Johnson D. E.","year":"2020","journal-title":"Nature Reviews Disease Primers"},{"issue":"3","key":"e_1_2_11_3_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung H.","year":"2021","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"20","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1158\/0008-5472.CAN-04-0960","article-title":"The Centrosomal Kinase Nek2 Displays Elevated Levels of Protein Expression in Human Breast Cancer","volume":"64","author":"Hayward D. G.","year":"2004","journal-title":"Cancer Research"},{"issue":"2","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/emboj\/17.2.470","article-title":"A Centrosomal Function for the Human Nek2 Protein Kinase, a Member of the NIMA Family of Cell Cycle Regulators","volume":"17","author":"Fry A. M.","year":"1998","journal-title":"EMBO Journal"},{"issue":"1","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.ccr.2012.12.001","article-title":"NEK2 Induces Drug Resistance Mainly Through Activation of Efflux Drug Pumps and Is Associated With Poor Prognosis in Myeloma and Other Cancers","volume":"23","author":"Zhou W.","year":"2013","journal-title":"Cancer Cell"},{"issue":"1","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12935-025-03644-x","article-title":"Overexpressed NEK2 Contributes to Progression and Cisplatin Resistance Through Activating the Wnt\/\u03b2\u2010Catenin Signaling Pathway in Cervical Cancer","volume":"25","author":"Haiye J.","year":"2025","journal-title":"Cancer Cell International"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-026-47174-6","article-title":"NEK2 Promotes Oral Squamous Cell Carcinoma Progression and Serves as a Diagnostic and Therapeutic Target","volume":"16","author":"Wu H.","year":"2026","journal-title":"Scientific Reports"},{"issue":"5","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial\u2010Mesenchymal Transitions in Development and Disease","volume":"139","author":"Thiery J. P.","year":"2009","journal-title":"Cell"},{"key":"e_1_2_11_10_1","article-title":"E2F1 Promotes LIHC Malignant Phenotype via NEK2\u2010Mediated Wnt\/\u03b2\u2010Catenin and Notch Activation and EMT","volume":"832","author":"Hong L.","year":"2026","journal-title":"Mutation Research"},{"issue":"20","key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"8393","DOI":"10.1158\/0008-5472.CAN-08-1915","article-title":"Small Molecule Targeting the Hec1\/Nek2 Mitotic Pathway Suppresses Tumor Cell Growth in Culture and in Animal","volume":"68","author":"Wu G.","year":"2008","journal-title":"Cancer Research"},{"issue":"8","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nri2586","article-title":"Structure and Signalling in the IL\u201017 Receptor Family","volume":"9","author":"Gaffen S. L.","year":"2009","journal-title":"Nature Reviews Immunology"},{"issue":"5","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nrc2628","article-title":"Tumour Necrosis Factor and Cancer","volume":"9","author":"Balkwill F.","year":"2009","journal-title":"Nature Reviews Cancer"},{"issue":"11","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1038\/sj.jid.5701015","article-title":"Desmosomes: New Perspectives on a Classic","volume":"127","author":"Green K. J.","year":"2007","journal-title":"Journal of Investigative Dermatology"},{"issue":"8","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1161\/CIRCRESAHA.119.314813","article-title":"Endothelial\u2010To\u2010Mesenchymal Transition","volume":"124","author":"Bischoff J.","year":"2019","journal-title":"Circulation Research"},{"issue":"3","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/nrc745","article-title":"New Functions for the Matrix Metalloproteinases in Cancer Progression","volume":"2","author":"Egeblad M.","year":"2002","journal-title":"Nature Reviews Cancer"},{"issue":"12","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.15252\/embr.201439246","article-title":"The Extracellular Matrix Modulates the Hallmarks of Cancer","volume":"15","author":"Pickup M. W.","year":"2014","journal-title":"EMBO Reports"},{"issue":"5","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nrc.2018.11","article-title":"The Molecular Landscape of Head and Neck Cancer","volume":"18","author":"Leemans C. R.","year":"2018","journal-title":"Nature Reviews Cancer"},{"issue":"2","key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.canlet.2005.06.017","article-title":"Nek2 Kinase in Chromosome Instability and Cancer","volume":"237","author":"Hayward D. G.","year":"2006","journal-title":"Cancer Letters"},{"issue":"2","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"352","DOI":"10.2741\/4212","article-title":"Nek2 and Plk4: Prognostic Markers, Drivers of Breast Tumorigenesis and Drug Resistance","volume":"19","author":"Marina M.","year":"2014","journal-title":"Frontiers in Bioscience"},{"issue":"4","key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.3892\/or.2016.5009","article-title":"Increased NEK2 in Hepatocellular Carcinoma Promotes Cancer Progression and Drug Resistance by Promoting PP1\/Akt and Wnt Activation","volume":"36","author":"Wen S.","year":"2016","journal-title":"Oncology Reports"},{"key":"e_1_2_11_22_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.gene.2022.147040","article-title":"NEK2 Is Associated With Poor Prognosis of Clear Cell Renal Cell Carcinoma and Promotes Tumor Cell Growth and Metastasis","volume":"851","author":"Feng X.","year":"2023","journal-title":"Gene"},{"issue":"2","key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1152\/physrev.00021.2018","article-title":"Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases","volume":"99","author":"Piera\u2010Velazquez S.","year":"2019","journal-title":"Physiological Reviews"},{"key":"e_1_2_11_24_1","doi-asserted-by":"crossref","first-page":"10243","DOI":"10.2147\/CMAR.S271109","article-title":"Overexpression of Cancer Upregulated Gene 2 (CUG2) Decreases Spry2 Through c\u2010Cbl, Leading to Activation of EGFR and \u03b2\u2010Catenin Signaling","volume":"12","author":"Yawut N.","year":"2020","journal-title":"Cancer Management and Research"},{"issue":"4","key":"e_1_2_11_25_1","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.immuni.2019.03.021","article-title":"The IL\u201017 Family of Cytokines in Health and Disease","volume":"50","author":"McGeachy M. J.","year":"2019","journal-title":"Immunity"},{"issue":"1","key":"e_1_2_11_26_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23010146","article-title":"Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression","volume":"23","author":"Niland S.","year":"2021","journal-title":"International Journal of Molecular Sciences"}],"container-title":["BioFactors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.70161","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biof.70161","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.70161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:31:54Z","timestamp":1792553514000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/biof.70161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/biof.70161"],"URL":"https:\/\/doi.org\/10.1002\/biof.70161","archive":["Portico"],"relation":{},"ISSN":["0951-6433","1872-8081"],"issn-type":[{"value":"0951-6433","type":"print"},{"value":"1872-8081","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-06-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70161"}}