头颈鳞状细胞癌（HNSCC）是最具侵袭性的肿瘤之一，需要更有效的预防和治疗方法。以往的研究发现蛋白O-岐酸转移酶1（POFUT1）的上调促进了癌变，然而，POFUT1在HNSCC中的潜在作用、潜在分子机制和生物学意义尚未进行研究。在本研究中，通过计算机辅助分析发现POFUT1可能是HNSCC的潜在癌基因。进一步使用数量实时聚合酶链式反应、Western blot分析和免疫组化方法对肿瘤和正常组织标本以及HNSCC细胞进行分析，发现与对照组相比，HNSCC临床肿瘤组织标本和细胞系中都明显过表达了POFUT1。体外研究揭示了POFUT1过表达能促进与癌增殖相关的表型，并且在HNSCC细胞中减少POFUT1表达则抑制了这些表型。进一步的异种移植实验证明，POFUT1在HNSCC中是一个癌基因。免疫组织化学分析人临床样本和癌细胞-脊神经节外体培养模型表明POFUT1的失调参与了HNSCC细胞的周围神经侵袭。这些结果表明POFUT1表达作为头颈癌患者的潜在预后标志物，并突显了它作为HNSCC治疗靶点的潜力，尽管还需要更多的分子线索来更好地定义POFUT1在HNSCC癌变中的功能。©2023 International Federation of Cell Biology.

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive neoplasms, which requires more effective prevention and treatment modalities. Previous studies found that protein O-fucosyltransferase 1 (POFUT1) upregulation promotes carcinogenesis, although the potential roles, underlying molecular mechanisms, and biological implications of POFUT1 in HNSCC were not investigated. In this study, in silico analyses referred POFUT1 as a potential oncogene in HNSCC. Further analysis of tumor and normal tissue samples as well as HNSCC cells with quantitative real-time 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 POFUT1 is an oncogene in vivo for HNSCC. Immunohistochemical analysis with human clinical samples and cancer cell-dorsal root ganglion ex-vivo 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 POFUT1 related to HNSCC carcinogenesis.© 2023 International Federation of Cell Biology.