Lewis(y) Promotes Migration of Oral Cancer Cells by Glycosylation of Epidermal Growth Factor Receptor

Aberrant glycosylation changes normal cellular functions and represents a specific hallmark of cancer. Lewis(y) (Le(y)) carbohydrate upregulation has been reported in a variety of cancers, including oral squamous cell carcinoma (OSCC). A high level of Le(y) expression is related to poor prognosis of patients with oral cancer. However, it is unclear how Le(y) mediates oral cancer progression. In this study, the role of Le(y) in OSCC was explored. Our data showed that Le(y) was upregulated in HSC-3 and OC-2 OSCC cell lines. Particularly, glycosylation of epidermal growth factor receptor (EGFR) with Le(y) was found in OC-2 cells, and this modification was absent upon inhibition of Le(y) synthesis. The absence of Le(y) glycosylation of EGFR weakened phosphorylation of AKT and ERK in response to epidermal growth factor (EGF). Additionally, EGF-triggered cell migration was reduced, but cell proliferation was not affected. Le(y) modification stabilized EGFR upon ligand activation. Conversely, absence of Le(y) glycosylation accelerated EGFR degradation. In summary, these results indicate that increased expression of Le(y) in OSCC cells is able to promote cell migration by modifying EGFR which in turn stabilizes EGFR expression and downstream signaling. Targeting Le(y) on EGFR could have a potential therapeutic effect on oral cancer.