1. Transcription factor SP1 regulates haptoglobin fucosylation via induction of GDP-fucose transporter 1 in the hepatoma cell line HepG2
- Author
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Jumpei Kondo, Natsumi Sakata, Koichi Morishita, Ayumu Hayashibara, Daisuke Sakon, Shinji Takamatsu, Nobuhiko Asakura, Takashi Suzuki, and Eiji Miyoshi
- Subjects
Fucosylation ,Haptoglobin ,Solute carrier family 35 member C1(SLC35C1) ,GDP-Fucose transporter 1 (GFT1) ,Specificity protein 1 (SP1) ,Cancer biomarker ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
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.
- Published
- 2022
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