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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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

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Polysaccharides
Tumors
Neoplasms
Integrins
Brain
Chemical activation
Cells
Dystroglycans
Brain Neoplasms
Focal Adhesion Protein-Tyrosine Kinases
Glucuronosyltransferase
Laminin
Assays
Complementary DNA
Kaplan-Meier Estimate
Carbohydrates
Glioma
Cell Movement
Antibodies
Injections

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Suzuki-Anekoji, M., Suzuki, M., Kobayashi, T., Sato, Y., Nakayama, J., Suzuki, A., ... 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

HNK-1 glycan functions as a tumor suppressor for astrocytic tumor. / Suzuki-Anekoji, Misa; Suzuki, Masami; Kobayashi, Tatsuya; Sato, Yoshiko; Nakayama, Jun; Suzuki, Atsushi; Bao, Xingfeng; Angata, Kiyohiko; Fukuda, Minoru.

In: Journal of Biological Chemistry, Vol. 286, No. 37, 16.09.2011, p. 32824-32833.

Research output: Contribution to journalArticle

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, vol. 286, no. 37, pp. 32824-32833. https://doi.org/10.1074/jbc.M111.245886
Suzuki-Anekoji M, Suzuki M, Kobayashi T, Sato Y, Nakayama J, Suzuki A et al. HNK-1 glycan functions as a tumor suppressor for astrocytic tumor. Journal of Biological Chemistry. 2011 Sep 16;286(37):32824-32833. https://doi.org/10.1074/jbc.M111.245886
Suzuki-Anekoji, Misa ; Suzuki, Masami ; Kobayashi, Tatsuya ; Sato, Yoshiko ; Nakayama, Jun ; Suzuki, Atsushi ; Bao, Xingfeng ; Angata, Kiyohiko ; Fukuda, Minoru. / HNK-1 glycan functions as a tumor suppressor for astrocytic tumor. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 37. pp. 32824-32833.
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