Transcription factor SP1 regulates haptoglobin fucosylation via induction of GDP-fucose transporter 1 in the hepatoma cell line HepG2

Fucosylation is involved in cancer and inflammation, and several fucosylated proteins, such as AFP-L3 for hepatocellular carcinoma, are used as cancer biomarkers. We previously reported an increase in serum fucosylated haptoglobin (Fuc-Hp) as a biomarker for several cancers, including pancreatic and colon cancer and hepatocellular carcinoma. The regulation of fucosylated protein production is a complex cellular process involving various fucosylation regulatory genes. In this report, we investigated the molecular mechanisms regulating Fuc-Hp production in cytokine-treated hepatoma cells using a partial least squares (PLS) regression model. We found that SLC35C1, which encodes GDP-fucose transporter 1 (GFT1), is the most responsible factor for Fuc-Hp production among various fucosylation regulatory genes. Furthermore, the transcription factor SP1 was essential in regulating SLC35C1 expression. We also found that an SP1 inhibitor was able to suppress Fuc-Hp production without affecting total Hp levels. Taken together, Fuc-Hp production was regulated by SP1 via induction of GFT1 in the hepatoma cell line HepG2.