論文

査読有り 国際誌
2020年5月22日

Enhancement of O‑linked N‑acetylglucosamine modification promotes metastasis in patients with colorectal cancer and concurrent type 2 diabetes mellitus

Oncology Letters
  • Yutaka Naka
  • ,
  • Toshihiko Okada
  • ,
  • Takatoshi Nakagawa
  • ,
  • Eiko Kobayashi
  • ,
  • Yuka Kawasaki
  • ,
  • Yasuyoshi Tanaka
  • ,
  • Hideki Tawa
  • ,
  • Yuki Hirata
  • ,
  • Ken Kawakami
  • ,
  • Kazuki Kakimoto
  • ,
  • Takuya Inoue
  • ,
  • Toshihisa Takeuchi
  • ,
  • Shinya Fukunishi
  • ,
  • Yoshinobu Hirose
  • ,
  • Kazuhisa Uchiyama
  • ,
  • Michio Asahi
  • ,
  • Kazuhide Higuchi

20
2
開始ページ
1171
終了ページ
1178
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3892/ol.2020.11665
出版者・発行元
Spandidos Publications

Reversible post-translational modification of serine and threonine residues by O-linked N-acetylglucosamine (O-GlcNAc), termed O-GlcNAcylation has been indicated to regulate the activities of a number of different proteins. Augmented O-GlcNAcylation contributes to the etiologies of type 2 diabetes mellitus (T2DM) and cancer. Moreover, diabetic conditions increase the risk of colorectal cancer. However, the effect of O-GlcNAcylation in patients with colorectal cancer and concurrent T2DM has not been elucidated. The current study evaluated the level of O-GlcNAcylation in patients with colorectal cancer with or without T2DM. Notably, O-GlcNAcylation levels were significantly higher in tissues from patients with T2DM compared with those in patients without T2DM, and higher in cancer tissues compared with corresponding adjacent tissues. O-GlcNAcylation and cancer stage were more strongly correlated in cancer tissues from patients with T2DM compared with those from patients without T2DM. Additionally, distant metastasis was significantly correlated with O-GlcNAcylation in cancer tissues from patients with T2DM. β-catenin levels in colorectal cancer tissues were the highest in patients with advanced-stage cancer and concurrent T2DM. In SW480 human colon cancer cells, thiamet G (TMG) treatment and OGA silencing, which increased O-GlcNAcylation, significantly increased β-catenin and SNAIL in high-glucose, but not during normal-glucose conditions. These data suggest that O-GlcNAcylation is closely associated with distant metastasis, most likely through upregulation of the β-catenin/SNAIL signaling pathway in colorectal cancer patients with T2DM.

リンク情報
DOI
https://doi.org/10.3892/ol.2020.11665
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32724357
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378307
ID情報
  • DOI : 10.3892/ol.2020.11665
  • ISSN : 1792-1074
  • eISSN : 1792-1082
  • PubMed ID : 32724357
  • PubMed Central 記事ID : PMC7378307

エクスポート
BibTeX RIS