Investigation of the relationship of POFUT1 gene with malign phenotypes and perineural invasion in human head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignant diseases and requires more effective prevention and treatment strategies. Previous studies revealed that POFUT1 overexpression 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 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 co-culture 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.