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Previous studies found that protein O\u2010fucosyltransferase 1 (<jats:italic>POFUT1<\/jats:italic>) upregulation promotes carcinogenesis, although the potential roles, underlying molecular mechanisms, and biological implications of <jats:italic>POFUT1<\/jats:italic> in HNSCC were not investigated. In this study, in silico analyses referred <jats:italic>POFUT1<\/jats:italic> as a potential oncogene in HNSCC. Further analysis of tumor and normal tissue samples as well as HNSCC cells with quantitative real\u2010time polymerase chain reaction, Western blot analysis, and immunohistochemistry showed significant overexpression of POFUT1 in HNSCC clinical tumor tissue specimens and cell lines compared to corresponding controls. In vitro investigations revealed that overexpression of POFUT1 promoted phenotypes associated with cancer aggressiveness and its knockdown in HNSCC cells suppressed those phenotypes. Further xenograft experiments demonstrated that <jats:italic>POFUT1<\/jats:italic> is an oncogene in vivo for HNSCC. Immunohistochemical analysis with human clinical samples and cancer cell\u2010dorsal root ganglion ex\u2010vivo coculture model showed that deregulation of POFUT1 is involved in the perineural invasion of HNSCC cells. These results suggest POFUT1 expression as a potential prognostic marker for patients with head and neck cancer and highlight its potential as a target for HNSCC therapy, although more molecular clues are needed to better define the functions of <jats:italic>POFUT1<\/jats:italic> related to HNSCC carcinogenesis.<\/jats:p>","DOI":"10.1002\/cbin.12085","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T03:36:32Z","timestamp":1693280192000},"page":"1950-1963","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Overexpression of POFUT1 promotes malignant phenotype and mediates perineural invasion in head and neck squamous cell carcinoma"],"prefix":"10.1002","volume":"47","author":[{"given":"Neslisah","family":"Barlak","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics Erzurum Technical University Erzurum Turkey"},{"name":"Molecular Cancer Biology Laboratory, High Technology Application and Research Center Erzurum Technical University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulnur","family":"Kusdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Erzurum Technical University Erzurum Turkey"},{"name":"Molecular Cancer Biology Laboratory, High Technology Application and Research Center Erzurum Technical University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasim","family":"Gumus","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Erzurum Technical University Erzurum Turkey"},{"name":"Molecular Cancer Biology Laboratory, High Technology Application and Research Center Erzurum Technical University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Gundogdu","sequence":"additional","affiliation":[{"name":"Department of Medical Pathology, Faculty of Medicine Ataturk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Hakan","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Brain and Nerve Surgery, Faculty of Medicine Ataturk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu","family":"Tatar","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Diseases, Faculty of Medicine Ataturk University Erzurum Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ittmann","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Immunology Baylor College of Medicine Houston Texas USA"},{"name":"Michael E. 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