title: Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells.
abstract: Protein glycosylation is an important posttranslational process, which regulates protein folding and functional expression. Studies have shown that abnormal glycosylation in tumor cells affects cancer progression and malignancy. In the current study, we have identified sialylated proteins using an alkynyl sugar probe in two different lung cancer cell lines, CL1-0 and CL1-5 with distinct invasiveness derived from the same parental cell line. Among the identified sialylated proteins, epidermal growth factor receptor (EGFR) was chosen to understand the effect of sialylation on its function. We have determined the differences in glycan sequences of EGFR in both cells and observed higher sialylation and fucosylation of EGFR in CL1-5 than in CL1-0. Further study suggested that overexpression of sialyltransferases in CL1-5 and α1,3-fucosyltransferases (FUT4 or FUT6) in CL1-5 and A549 cells would suppress EGFR dimerization and phosphorylation upon EGF treatment, as compared to the control and CL1-0 cells. Such modulating effects on EGFR dimerization were further confirmed by sialidase or fucosidase treatment. Thus, increasing sialylation and fucosylation could attenuate EGFR-mediated invasion of lung cancer cells. However, incorporation of the core fucose by α1,6-fucosylatransferase (FUT8) would promote EGFR dimerization and phosphorylation.
authors.affiliation: Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan.
authors.forename: Ying-Chih
authors.initials: YC
authors.lastname: Liu
authors.forename: Hsin-Yung
authors.initials: HY
authors.lastname: Yen
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Chein-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Ping-Fu
authors.initials: PF
authors.lastname: Cheng
authors.forename: Yi-Hsiu
authors.initials: YH
authors.lastname: Juan
authors.forename: Chung-Hsuan
authors.initials: CH
authors.lastname: Chen
authors.forename: Kay-Hooi
authors.initials: KH
authors.lastname: Khoo
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Hsu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D019281:Dimerization; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005643:Fucose / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D017931:DNA Primers; D011994:Recombinant Proteins; D012794:Sialic Acids; D005643:Fucose; D066246:ErbB Receptors