Liu Y.-C.Yen H.-Y.Chen C.-Y.Chen C.-H.Cheng P.-F.Juan Y.-H.Chen C.-H.Khoo K.-H.CHONG-JEN YUPAN-CHYR YANGHsu T.-L.Wong C.-H.2020-12-022020-12-0220110027-8424https://www.scopus.com/inward/record.uri?eid=2-s2.0-79960978002&doi=10.1073%2fpnas.1107385108&partnerID=40&md5=91e2a9aa3e883b0dfd0b08799a6fab40https://scholars.lib.ntu.edu.tw/handle/123456789/523634Protein 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. Wehave 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 EGFRmediated invasion of lung cancer cells. However, incorporation of the core fucose by α1,6- fucosylatransferase (FUT8) would promote EGFR dimerization and phosphorylation.[SDGs]SDG3alkynyl group; alpha 1,3 fucosyltransferase; alpha levo fucosidase; epidermal growth factor; epidermal growth factor receptor; glycan; sialidase; sialyltransferase; amino acid sequence; article; cancer cell; cancer cell culture; cell strain A549; cell strain CL1-0; cell strain CL1-5; controlled study; dimerization; fucosylation; human; human cell; lung cancer; priority journal; protein analysis; protein expression; protein function; protein induction; protein phosphorylation; sialylation; Amino Acid Sequence; Base Sequence; Binding Sites; Cell Line, Tumor; Dimerization; DNA Primers; Enzyme Activation; Fucose; Glycosylation; Humans; Lung Neoplasms; Models, Molecular; Molecular Sequence Data; Neoplasm Invasiveness; Protein Structure, Quaternary; Receptor, Epidermal Growth Factor; Recombinant Proteins; Sialic Acids; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionizationjournal article10.1073/pnas.1107385108217092632-s2.0-79960978002