title: Hypoxia inducible factor 1α down regulates cell surface expression of α1,2-fucosylated glycans in human pancreatic adenocarcinoma cells.
abstract: The α1,2-fucosyltransferase activity in pancreatic tumors is much lower compared to normal pancreatic tissue. Here we show that hypoxia inducible factor (HIF) 1α is constitutively expressed in the pancreatic cancer cell lines Pa-Tu-8988S and Pa-Tu-8988T and suppresses the expression of the α1,2-fucosyltransferase genes FUT1 and FUT2. Down regulation of HIF-1α expression resulted in elevated FUT1 and FUT2 transcript levels and an increased expression of α1,2-fucosylated glycan structures on the surface of these cells. In conclusion, our data are the first to identify HIF-1α as a suppressor of FUT1/2 expression, thereby regulating α1,2-fucosylation of cell-surface glycans.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Belo
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Andreas
authors.initials: A
authors.lastname: Maus
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Laan
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Tessa D
authors.initials: TD
authors.lastname: Nauta
authors.affiliation: Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Koolwijk
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands.
authors.forename: Boris
authors.initials: B
authors.lastname: Tefsen
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands. Electronic address: im.vandie@vumc.nl.
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011134:Polysaccharides / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D005643:Fucose; D005647:Fucosyltransferases; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011134:Polysaccharides; D012333:RNA, Messenger; D000097631:Galactoside 2-alpha-L-fucosyltransferase
keywords: Cancer; Fucosyltransferase; Glycosyltransferase; Hypoxia inducible factor 1 α (HIF-1α); Regulation of gene expression