Lectin ZG16p inhibits proliferation of human colorectal cancer cells via its carbohydrate-binding sites

Akiko Mito, Yukiko Nakano, Takako Saitoh, Sabine S.S. Gouraud, Yoshiki Yamaguchi, Toshiro Sato, Nobuo Sasaki, Kyoko Kojima-Aikawa

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Zymogen granule protein 16 (ZG16p) is a soluble lectin that binds to both mannose and heparin/ heparan sulfate. It is highly expressed in the human digestive tract and is secreted into the mucus. In this study, we investigated the effect of ZG16p on the proliferation of human colorectal cancer cells. Overexpression of ZG16p in Caco-2 cells decreased cell growth. Recombinant ZG16p markedly inhibited proliferation of Caco-2, LS174T, HCT116 and HCT15 cells. Caco-2 cell growth was not inhibited by two mutated ZG16p proteins, D151A and M5 (K36A, R37A, R53A, R55A and R79A) lacking mannose- and heparin-binding activities, respectively. Immunofluorescent cell staining revealed that ZG16p-D151A maintained its binding to the Caco-2 cell surface, whereas ZG16p-M5 failed to bind to the cells. These results suggest that ZG16p interacts with the cell surface via basic amino acids substituted in ZG16p-M5 and inhibits Caco-2 cell proliferation via Asp151. In addition, growth of patient-derived colorectal tumor organoids in a 3D intestinal stem cell system was suppressed by ZG16p but not by ZG16p-M5. Taken together, our findings indicate that ZG16p inhibits the growth of colorectal cancer cells via its carbohydrate-binding sites in vitro and ex vivo. In this study, a novel pathway in cancer cell growth regulation through cell surface carbohydrate chains is suggested.

Original languageEnglish
Pages (from-to)21-31
Number of pages11
JournalGlycobiology
Volume28
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Colorectal Neoplasms
Cell growth
Binding Sites
Cells
Carbohydrates
Caco-2 Cells
Mannose
Heparin
Growth
Basic Amino Acids
Enzyme Precursors
Heparitin Sulfate
Cell proliferation
Stem cells
Lectins
Tumors
Proteins
Organoids
HCT116 Cells
rat ZG16 protein

Keywords

  • Carbohydrate-binding sites
  • Cell proliferation
  • Colorectal cancer
  • Lectin
  • ZG16p

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mito, A., Nakano, Y., Saitoh, T., Gouraud, S. S. S., Yamaguchi, Y., Sato, T., ... Kojima-Aikawa, K. (2018). Lectin ZG16p inhibits proliferation of human colorectal cancer cells via its carbohydrate-binding sites. Glycobiology, 28(1), 21-31. https://doi.org/10.1093/glycob/cwx088

Lectin ZG16p inhibits proliferation of human colorectal cancer cells via its carbohydrate-binding sites. / Mito, Akiko; Nakano, Yukiko; Saitoh, Takako; Gouraud, Sabine S.S.; Yamaguchi, Yoshiki; Sato, Toshiro; Sasaki, Nobuo; Kojima-Aikawa, Kyoko.

In: Glycobiology, Vol. 28, No. 1, 01.01.2018, p. 21-31.

Research output: Contribution to journalArticle

Mito, A, Nakano, Y, Saitoh, T, Gouraud, SSS, Yamaguchi, Y, Sato, T, Sasaki, N & Kojima-Aikawa, K 2018, 'Lectin ZG16p inhibits proliferation of human colorectal cancer cells via its carbohydrate-binding sites', Glycobiology, vol. 28, no. 1, pp. 21-31. https://doi.org/10.1093/glycob/cwx088
Mito, Akiko ; Nakano, Yukiko ; Saitoh, Takako ; Gouraud, Sabine S.S. ; Yamaguchi, Yoshiki ; Sato, Toshiro ; Sasaki, Nobuo ; Kojima-Aikawa, Kyoko. / Lectin ZG16p inhibits proliferation of human colorectal cancer cells via its carbohydrate-binding sites. In: Glycobiology. 2018 ; Vol. 28, No. 1. pp. 21-31.
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