O-GlcNAcylation in oral squamous cell carcinoma

BackgroundTwo post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked -N-acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC). Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading. MethodsThirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFR(tyr1173), and anti-phosphorylated-Akt(ser473) antibodies following standard immunohistochemistry. The immunohistochemical (IHC) score was determined using the Fromowitz standard. Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody. ResultsThe median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFR(tyr1173) and phosphorylated-Akt(ser473) were significantly higher in OSCC than normal tissues (P<.001 and P<.01, respectively). Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ. In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFR(tyr1173) and phosphorylated-Akt(ser473) (P<.01 and P<.001, respectively). The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading. ConclusionUnlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.