title: Suppression of FUT1 attenuates cell proliferation in the HER2-overexpressing             cancer cell line NCI-N87.
abstract: Lewis Y (LeY) antigen is an oligosaccharide that is highly expressed at             the cell surface in various human cancers. Increased LeY expression activates             epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor             2 (HER2) and promotes cell proliferation in EGFR-overexpressing cells. However,             the effect of downregulation of LeY expression on cell proliferation in HER2-overexpressing             cells remains unknown. FUT1 encodes α1,2-fucosyltransferase, a key enzyme for             LeY synthesis. We knocked down FUT1 by short interfering RNA (siRNA) in four HER2-overexpressing             human cancer cell lines, including NCI-N87, MKN7, SKBr3 and BT474. We investigated             whether downregulation of LeY and alteration in the glycosylation status of these             cells affect cell proliferation and HER2 activation. Knocking down FUT1 expression             markedly inhibited proliferation of NCI-N87, which highly expressed EGFR and was             sensitive to EGFR deprivation. Furthermore, FUT1 siRNA downregulated the total             amount of HER2 protein, phosphorylation of HER2 and EGFR, and phosphorylation             of extracellular signal-regulated kinase (ERK) in this cell line. Moreover, the             marked downregulation of phosphorylation of HER2 and ERK was observed following             short-time EGF-stimulation. These effects were not observed in the other three             cell lines. Our results suggest that knockdown of FUT1 downregulates HER2 signaling             via EGFR downregulation. FUT1 may serve as a new molecular target for HER2-overexpressing             human cancers with activated EGFR signaling.
authors.affiliation: Department of Clinical Oncology, Institute of Development, Aging                     and Cancer, Tohoku University, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Kawai
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kato
authors.forename: Hiroo
authors.initials: H
authors.lastname: Imai
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Okada
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D049109:Cell Proliferation; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005647:Fucosyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000235:genetics / Q000378:metabolism*; D054547:National Cancer Institute (U.S.); D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014481:United States; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D005647:Fucosyltransferases; D007983:Lewis Blood Group Antigens; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C094162:Lewis Y antigen; C512478:EGFR protein, human; C508053:ERBB2 protein, human