Exp Mol Med.
2018 Feb;50(2):e443. 10.1038/emm.2017.267.
Silencing of peroxiredoxin II by promoter methylation is necessary for the survival and migration of gastric cancer cells
- Affiliations
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- 1Department of Life Sciences, Ewha Womans University, Seoul, Korea. kangsw@ewha.ac.kr
- 2Research Center for Cell Homeostasis, Ewha Womans University, Seoul, Korea.
- 3Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.
- 4Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Korea.
- 5Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Korea.
- KMID: 2440025
- DOI: http://doi.org/10.1038/emm.2017.267
Abstract
- Peroxiredoxin (Prx), a family of ubiquitous thiol peroxidases, functions as a redox signaling regulator that controls cellular Hâ‚‚Oâ‚‚ in mammalian cells and has recently received attention for being overexpressed in various cancer types. In this study, we show that Prx type II (PrxII) is rather silenced in gastric cancer cells. PrxII expression is severely downregulated in 9 out of the 28 gastric cancer cell lines. Strikingly, PrxII expression is completely lost in three cell lines, MKN28, MKN74 and SNU484. Loss of PrxII expression is due to DNA methyltransferase 1-dependent methylation at the promoter region of the PrxII gene. Restoration of PrxII expression using a retroviral system markedly reduces the colony-forming ability and migratory activity of both MKN28 and SNU484 cells by inhibiting Src kinase. Mechanistically, PrxII peroxidase activity is essential for regulating gastric cancer cell migration. Bioinformatics analysis from The Cancer Genome Atlas stomach cancer data (STAD) revealed significantly low PrxII expression in gastric cancer patients and a negative correlation between PrxII expression and methylation levels. More importantly, low PrxII expression also strongly correlates with poor survival in cancer patients. Thus our study suggests that PrxII may be the first thiol peroxidase that simultaneously regulates both survival and metastasis in gastric cancer cells with high clinical relevance.
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