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

• PDAC and colon cancer (CRC) cell lines constitutively express HIF-1α.
• HIF-1α inhibition enhances cell surface α1,2-fucosylation on PDAC and CRC cells.
• Inhibition of HIF-1α enhances FUT1 and FUT2 transcripts in PDAC and CRC cells.
• Knock down of HIF-1α increases FUT1/2 expression and α1,2-fucosylation in PaTu-T.
• HIF-1α suppresses FUT1/2 expression, thus regulating cell surface α1,2-fucosylation.

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.