Cisplatin enhances protein O‑GlcNAcylation by altering the activity of OGT, OGA and AMPK in human non‑small cell lung cancer cells

  • Authors:
    • Di Wang
    • Jiaan Wu
    • Dandan Wang
    • Xiaoyan Huang
    • Naining Zhang
    • Yikang Shi
  • View Affiliations

  • Published online on: April 8, 2021     https://doi.org/10.3892/ijo.2021.5207
  • Article Number: 27
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Abstract

O‑GlcNAcylation is a dynamic and reversible post‑translational modification of proteins that is modulated by O‑GlcNAc transferase (OGT) and O‑GlcNAcase (OGA). Alterations in the protein expression of O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) can be induced by multiple factors. However, little is known of the effects of chemotherapeutic agents on O‑GlcNAcylation and the relevant molecular mechanisms in cancer cells. In the present study, to investigate whether cisplatin alters protein O‑GlcNAcylation and to explore whether protein O‑GlcNAc modification affects the antitumor activity of cisplatin, experiments were performed in vitro and in vivo. The results indicated that cisplatin treatment resulted in an enhancement of global protein O‑GlcNAc levels in the H1299, Hep G2 and MCF‑7 cells in vitro and in vivo. Cisplatin upregulated the protein and mRNA expression levels of OGT and OGA in H1299 cells. Moreover, cisplatin induced the significant enhancement of the enzymatic activity of OGT in H1299 cells. On the contrary, the activation of OGA decreased in response to cisplatin exposure in H1299 cells. Cisplatin inhibited the activity of AMP‑activated protein kinase (AMPK) by decreasing the AMP/ATP ratio. The present study also revealed that the decreased AMPK activation inhibited glutamine‑fructose‑6‑phosphate aminotransferase (isomerizing) 1 (GFAT1) phosphorylation and subsequently promoted the activity of GFAT1. Cisplatin‑induced GFAT1 activation elevated the production of the donor substrate, uridine 5‑diphospho‑N‑acetylglucosamine (UDP‑GlcNAc). However, alterations in the O‑GlcNAc levels by the inhibition of OGT and OGA did not affect the sensitivity of lung cancer cells to cisplatin. On the whole, the present study demonstrates that cisplatin enhances protein O‑GlcNAcylation by altering the activity of OGT, OGA and AMPK in vitro and in vivo.
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June-2021
Volume 58 Issue 6

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Spandidos Publications style
Wang D, Wu J, Wang D, Huang X, Zhang N and Shi Y: Cisplatin enhances protein <em>O</em>‑GlcNAcylation by altering the activity of OGT, OGA and AMPK in human non‑small cell lung cancer cells. Int J Oncol 58: 27, 2021
APA
Wang, D., Wu, J., Wang, D., Huang, X., Zhang, N., & Shi, Y. (2021). Cisplatin enhances protein <em>O</em>‑GlcNAcylation by altering the activity of OGT, OGA and AMPK in human non‑small cell lung cancer cells. International Journal of Oncology, 58, 27. https://doi.org/10.3892/ijo.2021.5207
MLA
Wang, D., Wu, J., Wang, D., Huang, X., Zhang, N., Shi, Y."Cisplatin enhances protein <em>O</em>‑GlcNAcylation by altering the activity of OGT, OGA and AMPK in human non‑small cell lung cancer cells". International Journal of Oncology 58.6 (2021): 27.
Chicago
Wang, D., Wu, J., Wang, D., Huang, X., Zhang, N., Shi, Y."Cisplatin enhances protein <em>O</em>‑GlcNAcylation by altering the activity of OGT, OGA and AMPK in human non‑small cell lung cancer cells". International Journal of Oncology 58, no. 6 (2021): 27. https://doi.org/10.3892/ijo.2021.5207