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

The alpha 1,2-fucosyltransferase activity in pancreatic tumors is much lower compared to normal pancreatic tissue. Here we show that hypoxia inducible factor (HIF) 1 alpha is constitutively expressed in the pancreatic cancer cell lines Pa-Tu-8988S and Pa-Tu-8988T and suppresses the expression of the alpha 1,2-fucosyltransferase genes FUT1 and FUT2. Down regulation of HIF-1 alpha expression resulted in elevated FUT1 and FUT2 transcript levels and an increased expression of alpha 1,2-fucosylated glycan structures on the surface of these cells. In conclusion, our data are the first to identify HIF-1 alpha as a suppressor of FUT1/2 expression, thereby regulating alpha 1,2-fucosylation of cell-surface glycans. (C) 2015 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.