title: 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.
authors: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan; Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan.
authors: Wei-Ling
authors: WL
authors: Lin
authors: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan; Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan.
authors: Yi-Shiuan
authors: YS
authors: Lin
authors: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan; Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan.
authors: Guey-Yueh
authors: GY
authors: Shi
authors: Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors: Chuan-Fa
authors: CF
authors: Chang
authors: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan; Cardiovascular Research Center, National Cheng Kung University, Tainan, Taiwan.
authors: Hua-Lin
authors: HL
authors: Wu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000502:physiology; D007983:Lewis Blood Group Antigens / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases