The mucin-type glycosylating enzyme polypeptide N-acetylgalactosaminyltransferase 14 promotes the migration of ovarian cancer by modifying mucin 13

Oncol Rep. 2013 Aug;30(2):667-76. doi: 10.3892/or.2013.2493. Epub 2013 May 24.

Abstract

A high expression of O-glycosylated proteins is one of the prominent characteristics of ovarian carcinoma cells associated with cell migration, which would be attributed to the upregulated expression of glycosyltransferases. Therefore, elucidating glycosyltransferases and their substrates may improve our understanding of their roles in tumor metastasis. In the present study, we reported that knockdown of polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14) by small interfering RNA significantly suppressed the cell migration and altered cellular morphology. Immunoprecipitation and western blot analyses indicated that GALNT14 contributed to the glycosylation of transmembrane mucin 13 (MUC13), which was significantly higher in ovarian cancer cells compared with the normal/benign ovary tissues. Furthermore, interleukin-8 (IL-8), which could regulate the migration ability of epithelial ovarian cancer (EOC) cells, had no remarkable effect on the expression of GALNT14 and the tumor-associated carbohydrate epitope Tn antigen. In addition, extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor modulated the expression levels of GALNT14. Our findings provide evidence that GALNT14 may contribute to ovarian carcinogenesis through aberrant glycosylation of MUC13, but not through the IL-8 pathway. These data provide novel insights into understanding the function of MUC13 on neoplasm metastasis and may aid in the development of new anticancer drugs for EOC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Tumor-Associated, Carbohydrate / genetics
  • Antigens, Tumor-Associated, Carbohydrate / metabolism
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology*
  • Female
  • Glycosylation
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • MAP Kinase Signaling System / genetics
  • Mucins / genetics*
  • Mucins / metabolism*
  • N-Acetylgalactosaminyltransferases / genetics*
  • N-Acetylgalactosaminyltransferases / metabolism*
  • Neoplasm Metastasis
  • Neoplasms, Glandular and Epithelial / enzymology*
  • Neoplasms, Glandular and Epithelial / genetics
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / enzymology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Interleukin-8
  • MUC13 protein, human
  • Mucins
  • Tn antigen
  • N-Acetylgalactosaminyltransferases
  • polypeptide N-acetylgalactosaminyltransferase