Lewisy Promotes Migration of Oral Cancer Cells by Glycosylation of Epidermal Growth Factor Receptor

Abstract

Aberrant glycosylation changes normal cellular functions and represents a specific hallmark of cancer. Lewisy (Ley) carbohydrate upregulation has been reported in a variety of cancers, including oral squamous cell carcinoma (OSCC). A high level of Ley expression is related to poor prognosis of patients with oral cancer. However, it is unclear how Ley mediates oral cancer progression. In this study, the role of Ley in OSCC was explored. Our data showed that Ley was upregulated in HSC-3 and OC-2 OSCC cell lines. Particularly, glycosylation of epidermal growth factor receptor (EGFR) with Ley was found in OC-2 cells, and this modification was absent upon inhibition of Ley synthesis. The absence of Ley 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. Ley modification stabilized EGFR upon ligand activation. Conversely, absence of Ley glycosylation accelerated EGFR degradation. In summary, these results indicate that increased expression of Ley in OSCC cells is able to promote cell migration by modifying EGFR which in turn stabilizes EGFR expression and downstream signaling. Targeting Ley on EGFR could have a potential therapeutic effect on oral cancer.

miR-200b inhibits proliferation and metastasis of breast cancer by targeting fucosyltransferase IV and α1,3-fucosylated glycans

“…EGFR is a scaffold carrying α1,3-fucosylation, particularly the LeY epitope. 34 Based on the above results showing that FUT4 is a potential target for miR-200b that may regulate its expression, we hypothesized that miR-200b altered LeY synthesis and EGFR activation. The results of a blotting analysis showed that miR-200b mimics transfection induced a decreased expression of α1,3-fucosylation of glycoproteins by Lotus Tetragonolobus Lectin (LTL) (which specifically recognizes and binds to α1,3-fucosylated glycans) blotting analysis ( Figures 6a and b ), whereas Anti-miR-200b facilitated cell surface α1,3-fucosylation synthesis.…”

“…After confirmation of the whole α1,3-fucosylation alteration by miR-200b transfection, we further selected LeY as a representative of α1,3-fucosylated glycans to analyze the effect of miR-200b. LeY, which contains an α1,3-fucosylation epitope is carried by many glycoproteins, including EGFR, 34 CD44 51 and MUC6, 52 on the cancer cells’ surface. EGFR is closely correlated with cancer cells’ proliferation and metastasis via the activation of EGFR and downstream signaling pathways.…”

High expressions of BCL6 and Lewis y antigen are correlated with high tumor burden and poor prognosis in epithelial ovarian cancer

“…36 Increased expression of Lewis y promotes cell proliferation and migration through activation of EGFR signal pathway. 15,50,51 Accordingly, there is a good possibility that Lewis y regulates the expression of CD44 via BCL6 by activation of EGFR signal to enhance the malignant behaviors in ovarian cancer, whereas the mechanisms are still warranted more in-depth and concentrated investigations.…”

Regulation of cell migration via the EGFR signaling pathway in oral squamous cell carcinoma cells

“…EGFR stimulation induces cell migration through the activation of matrix metalloproteinases (MMPs) (24), signal transducer and activator of transcription 3 (STAT3) (25,26) or the MEK/ERK and PI3K signaling pathways (9), and may be associated with an epithelial-mesenchymal transition (EMT)-like phenotype (27). Furthermore, cross-talk between EGFR and G-protein-coupled receptors contributes to cell migration (28,29).…”