Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: Downregulation of ST6GalNAc VI in renal cancers

Motohiro Senda, Akihiro Ito, Akiko Tsuchida, Tomoko Hagiwara, Tsuguhiro Kaneda, Yoko Nakamura, Kenji Kasama, Makoto Kiso, Kazuhiro Yoshikawa, Yoko Katagiri, Yoshinari Ono, Manabu Ogiso, Takeshi Urano, Keiko Furukawa, Shinichi Oshima, Koichi Furukawa

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28 Citations (Scopus)

Abstract

Although disialyl glycosphingolipids such as GD3 and GD2 have been considered to be associated with malignant tumours, whether branched-type disialyl glycosphingolipids show such an association is not well understood. We investigated the sialyltransferases responsible for the biosynthesis of DSGG (disialylgalactosylgloboside) from MSGG (monosialylgalactosylgloboside). Among six GalNAc:α2,6-sialyltransferases cloned to date, we focused on ST6GalNAc III, V and VI, which utilize sialylglycolipids as substrates. In vitro enzyme analyses revealed that ST6GalNAc III and VI generated DSGG from MSGG with V max/Km values of 1.91 and 4.16 respectively. Transfection of the cDNA expression vectors for these enzymes resulted in DSGG expression in a renal cancer cell line. Although both ST6GalNAc III and VI genes were expressed in normal kidney cells, the expression profiles of ST6GalNAc VI among 20 renal cancer cell lines correlated clearly with those of DSGG, suggesting that the sialyltransferase involved in the synthesis of DSGG in the kidney is ST6GalNAc-VI. ST6GalNAc-VI and DSGG were found in proximal tubule epithelial cells in normal kidney tissues, while they were downregulated in renal cancer cell lines and cancer tissues. All these findings indicated that DSGG was suppressed during the malignant transformation of the proximal tubules as a maturation arrest of glycosylation.

Original languageEnglish
Pages (from-to)459-470
Number of pages12
JournalBiochemical Journal
Volume402
Issue number3
DOIs
Publication statusPublished - 2007 Mar 15

Keywords

  • Globo-series
  • Glycolipid
  • Renal cancer
  • Sialyltransferase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Senda, M., Ito, A., Tsuchida, A., Hagiwara, T., Kaneda, T., Nakamura, Y., Kasama, K., Kiso, M., Yoshikawa, K., Katagiri, Y., Ono, Y., Ogiso, M., Urano, T., Furukawa, K., Oshima, S., & Furukawa, K. (2007). Identification and expression of a sialyltransferase responsible for the synthesis of disialylgalactosylgloboside in normal and malignant kidney cells: Downregulation of ST6GalNAc VI in renal cancers. Biochemical Journal, 402(3), 459-470. https://doi.org/10.1042/BJ20061118