HNK-1 glycan functions as a tumor suppressor for astrocytic tumor

Misa Suzuki-Anekoji, Masami Suzuki, Tatsuya Kobayashi, Yoshiko Sato, Jun Nakayama, Atsushi Suzuki, Xingfeng Bao, Kiyohiko Angata, Minoru Fukuda

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9 Citations (Scopus)

Abstract

Astrocytic tumor is the most prevalent primary brain tumor. However, the role of cell surface carbohydrates in astrocytic tumor invasion is not known. In a previous study, we showed that polysialic acid facilitates astrocytic tumor invasion and thereby tumor progression. Here, we examined the role of HNK-1 glycan in astrocytic tumor invasion. A Kaplan-Meier analysis of 45 patients revealed that higher HNK-1 expression levels were positively associated with increased survival of patients. To determine the role of HNK-1 glycan, we transfected C6 glioma cells, which lack HNK-1 glycan expression, with β1,3-glucuronyltransferase-P cDNA, generating HNK-1-positive cells. When these cells were injected into the mouse brain, the resultant tumors were 60% smaller than tumors emerging from injection of the mock-transfected HNK-1-negative C6 cells. HNK-1-positive C6 cells also grew more slowly than mock-transfected C6 cells in anchorage-dependent and anchorage-independent assays. C6-HNK-1 cells migrated well after treatment of anti-β1 integrin antibody, whereas the same treatment inhibited cell migration of mock-transfected C6 cells. Similarly, α-dystroglycan containingHNK-1glycan is different from those containing the laminin-binding glycans, supporting the above conclusion that C6-HNK-1 cells migrate independently from β1-integrin-mediated signaling. Moreover, HNK-1-positive cells exhibited attenuated activation of ERK 1/2 compared with mock-transfected C6 cells, whereas focal adhesion kinase activation was equivalent in both cell types. Overall, these results indicate that HNK-1 glycan functions as a tumor suppressor.

Original languageEnglish
Pages (from-to)32824-32833
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number37
DOIs
Publication statusPublished - 2011 Sep 16

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Suzuki-Anekoji, M., Suzuki, M., Kobayashi, T., Sato, Y., Nakayama, J., Suzuki, A., Bao, X., Angata, K., & Fukuda, M. (2011). HNK-1 glycan functions as a tumor suppressor for astrocytic tumor. Journal of Biological Chemistry, 286(37), 32824-32833. https://doi.org/10.1074/jbc.M111.245886