論文

査読有り 国際誌
2020年1月15日

O-GlcNAcylation-mediated degradation of FBXL2 stabilizes FOXM1 to induce cancer progression.

Biochemical and biophysical research communications
  • Yasuhiro Ueda
  • ,
  • Kazumasa Moriwaki
  • ,
  • Toshihisa Takeuchi
  • ,
  • Kazuhide Higuchi
  • ,
  • Michio Asahi

521
3
開始ページ
632
終了ページ
638
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2019.10.164

O-GlcNAcylation is a dynamic and reversible post-translational modification of cytonuclear molecules that regulates cellular signaling. Elevated O-GlcNAcylation is a general property of cancer and plays a critical role in cancer progression. We previously showed that the expression of FOXM1, a critical oncogenic transcription factor widely overexpressed in solid tumors, was elevated in MKN45 cells, a human gastric cancer cell line, by the O-GlcNAcase inhibitor Thiamet G (TMG), which induces augmented O-GlcNAcylation. Here, we identified FBXL2 E3 ubiquitin ligase as a new target of O-GlcNAcylation. Consistent with the results in MKN45 cells, FOXM1 expression was increased, accompanied by its decreased ubiquitination and degradation by TMG in the other gastric cancer cell lines, including NUGC-3 cells. We found that FBXL2 ubiquitinated FOXM1, and the interaction with FBXL2 and ubiquitination of FOXM1 were reduced by TMG in NUGC-3 cells. Interestingly, FBXL2 was also ubiquitinated, which was promoted by TMG in the cells. Moreover, FOXM1 expression and cell proliferation were reduced in FBXL2-induced NUGC-3 cells, and the reductions were attenuated by TMG, indicating that FOXM1 was stabilized by O-GlcNAcylation-mediated degradation of FBXL2 to induce cancer progression. These data suggest that elevated O-GlcNAcylation contributes to cancer progression by suppressing FBXL2-mediated degradation of FOXM1.

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2019.10.164
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31679690
ID情報
  • DOI : 10.1016/j.bbrc.2019.10.164
  • ISSN : 0006-291X
  • PubMed ID : 31679690

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