Hypoxia inducible factor 1α down regulates cell surface expression of α1,2-fucosylated glycans in human pancreatic adenocarcinoma cells

Ana I Belo; Sandra J van Vliet; Andreas Maus; Lisa C Laan; Tessa D Nauta; Pieter Koolwijk; Boris Tefsen; Irma van Die

doi:10.1016/j.febslet.2015.07.035

Hypoxia inducible factor 1α down regulates cell surface expression of α1,2-fucosylated glycans in human pancreatic adenocarcinoma cells

Ana I Belo
, Sandra J van Vliet
, Andreas Maus
, Lisa C Laan
, Tessa D Nauta
, Pieter Koolwijk
, Boris Tefsen
, Irma van Die

Amsterdam University Medical Center

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	2359-2366
Number of pages	8
Journal	FEBS Letters
Volume	589
Issue number	18
DOIs	https://doi.org/10.1016/j.febslet.2015.07.035
Publication status	Published - 19 Aug 2015
Externally published	Yes

Bibliographical note

Keywords

Adenocarcinoma/pathology
Cell Line, Tumor
Down-Regulation
Fucose/metabolism
Fucosyltransferases/genetics
Gene Expression Regulation, Neoplastic
Glycosylation
Humans
Hypoxia-Inducible Factor 1, alpha Subunit/genetics
Pancreatic Neoplasms/pathology
Polysaccharides/metabolism
RNA, Messenger/genetics
Galactoside 2-alpha-L-fucosyltransferase

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.febslet.2015.07.035

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@article{b8280e06277249a6b2759266930f7220,

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.",

keywords = "Adenocarcinoma/pathology, Cell Line, Tumor, Down-Regulation, Fucose/metabolism, Fucosyltransferases/genetics, Gene Expression Regulation, Neoplastic, Glycosylation, Humans, Hypoxia-Inducible Factor 1, alpha Subunit/genetics, Pancreatic Neoplasms/pathology, Polysaccharides/metabolism, RNA, Messenger/genetics, Galactoside 2-alpha-L-fucosyltransferase",

author = "Belo, \{Ana I\} and \{van Vliet\}, \{Sandra J\} and Andreas Maus and Laan, \{Lisa C\} and Nauta, \{Tessa D\} and Pieter Koolwijk and Boris Tefsen and \{van Die\}, Irma",

note = "Copyright {\textcopyright} 2015. Published by Elsevier B.V.",

year = "2015",

month = aug,

day = "19",

doi = "10.1016/j.febslet.2015.07.035",

language = "English",

volume = "589",

pages = "2359--2366",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

number = "18",

}

TY - JOUR

T1 - Hypoxia inducible factor 1α down regulates cell surface expression of α1,2-fucosylated glycans in human pancreatic adenocarcinoma cells

AU - Belo, Ana I

AU - van Vliet, Sandra J

AU - Maus, Andreas

AU - Laan, Lisa C

AU - Nauta, Tessa D

AU - Koolwijk, Pieter

AU - Tefsen, Boris

AU - van Die, Irma

PY - 2015/8/19

Y1 - 2015/8/19

N2 - 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.

AB - 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.

KW - Adenocarcinoma/pathology

KW - Cell Line, Tumor

KW - Down-Regulation

KW - Fucose/metabolism

KW - Fucosyltransferases/genetics

KW - Gene Expression Regulation, Neoplastic

KW - Glycosylation

KW - Humans

KW - Hypoxia-Inducible Factor 1, alpha Subunit/genetics

KW - Pancreatic Neoplasms/pathology

KW - Polysaccharides/metabolism

KW - RNA, Messenger/genetics

KW - Galactoside 2-alpha-L-fucosyltransferase

U2 - 10.1016/j.febslet.2015.07.035

DO - 10.1016/j.febslet.2015.07.035

M3 - Article

C2 - 26232512

SN - 0014-5793

VL - 589

SP - 2359

EP - 2366

JO - FEBS Letters

JF - FEBS Letters

IS - 18

ER -

Hypoxia inducible factor 1α down regulates cell surface expression of α1,2-fucosylated glycans in human pancreatic adenocarcinoma cells

Abstract

Bibliographical note

Keywords

UN SDGs

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