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: Cancer; Fucosyltransferase; Glycosyltransferase; Hypoxia inducible factor 1 α (HIF-1α); Regulation of gene expression.