{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:29:32Z","timestamp":1790630972092,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 112\u20102314\u2010B\u2010002\u2010100"],"award-info":[{"award-number":["NSTC 112\u20102314\u2010B\u2010002\u2010100"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022294","name":"National Taiwan University Hospital Yunlin Branch","doi-asserted-by":"publisher","award":["NTUHYL 113\u2010F003"],"award-info":[{"award-number":["NTUHYL 113\u2010F003"]}],"id":[{"id":"10.13039\/501100022294","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n The divergent loop structures of nicotinic acetylcholine receptor (nAChR)\n \u03b1<\/jats:italic>\n 3,\n \u03b1<\/jats:italic>\n 5, and\n \u03b1<\/jats:italic>\n 7 subunits (encoded by\n CHRNA3<\/jats:italic>\n ,\n CHRNA5<\/jats:italic>\n , and\n CHRNA7<\/jats:italic>\n ) are involved in kinase phosphorylation and signal transduction, potentially affecting oral squamous cell carcinoma (OSCC), the most common head and neck cancer (HNC). However, their specific roles in OSCC remain unclear.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We integrated analyses of SCC\u20104 tongue cancer cells with\n CHRNA<\/jats:italic>\n overexpression, immunohistochemistry of OSCC pathological specimens, and data from the cancer genome atlas (TCGA), DepMap, and Puram 2017 to assess\n CHRNA3<\/jats:italic>\n ,\n CHRNA5<\/jats:italic>\n , and\n CHRNA7<\/jats:italic>\n in OSCC\/HNC.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In OSCC,\n CHRNA3<\/jats:italic>\n ,\n CHRNA5<\/jats:italic>\n , and\n CHRNA7<\/jats:italic>\n expression interacted with epithelial\u2013mesenchymal transition (EMT) markers and correlated with invasive patterns.\n CHRNA3<\/jats:italic>\n reduced epithelial and enhanced mesenchymal traits, supporting EMT.\n CHRNA5<\/jats:italic>\n further promoted mesenchymal features, was linked to disseminated tumor patterns, and predicted poor prognosis.\n CHRNA7<\/jats:italic>\n enhanced both epithelial and mesenchymal markers, maintaining a hybrid EMT state. In HNC, bioinformatic analyses revealed that\n CHRNA3<\/jats:italic>\n preserved ion channel activity,\n CHRNA5<\/jats:italic>\n promoted DNA replication, reduced adhesion, suppressed antigen presentation, and induced hypomethylation and miRNA overexpression, while\n CHRNA7<\/jats:italic>\n promoted differentiation with variable effects on adhesion and antigen presentation. In DepMap HNC cell lines, high\n CHRNA3<\/jats:italic>\n \/\n CHRNA5<\/jats:italic>\n and low\n CHRNA7<\/jats:italic>\n expression were associated with resistance to most inhibitors. Epidermal growth factor receptor (EGFR) inhibitors were effective in\n CHRNA3<\/jats:italic>\n \/\n CHRNA<\/jats:italic>\n 7\u2010high HNC, whereas cyclin\u2010dependent kinase (CDK) inhibitors were effective in\n CHRNA5<\/jats:italic>\n \u2010high HNC.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Differential expression of\n CHRNA3<\/jats:italic>\n ,\n CHRNA<\/jats:italic>\n 5, and\n CHRNA7<\/jats:italic>\n indicates different EMT states in OSCC\/HNC, influencing proliferation, differentiation, cell adhesion, immune reactions, and treatment efficacy, and warrants further experimental validation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cam4.71358","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:07:06Z","timestamp":1762520826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Biological and Prognostic Implications of the Nicotinic Acetylcholine Receptor\n \u03b1<\/i>\n 3,\n \u03b1<\/i>\n 5, and\n \u03b1<\/i>\n 7 Subunits in Oral Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6562-1711","authenticated-orcid":false,"given":"Chi\u2010Maw","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Otolaryngology National Taiwan University Hospital, Yun\u2010Lin Branch Yun\u2010Lin Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long\u2010Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pathology National Taiwan University Hospital, Yun\u2010Lin Branch Yun\u2010Lin Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tseng\u2010Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology National Taiwan University Hospital and National Taiwan University, College of Medicine Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Ling","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Biotechnology National Formosa University Yun\u2010Lin Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bor\u2010Luen","family":"Chiang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medicine, College of Medicine National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41415-022-5166-x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00224-3"},{"issue":"1","key":"e_1_2_11_4_1","first-page":"66","article-title":"Novel Pathways and Mechanism of Nicotine\u2010Induced Oral 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