Reactive oxygen species-induced autophagic degradation of helicobacter pylori CagA is specifically suppressed in cancer stem-like cells

Hitoshi Tsugawa, Hidekazu Suzuki, Hideyuki Saya, Masanori Hatakeyama, Toshiya Hirayama, Kenro Hirata, Osamu Nagano, Juntaro Matsuzaki, Toshifumi Hibi

研究成果: Article査読

144 被引用数 (Scopus)

抄録

Sustained expression of CagA, the type IV secretion effector of Helicobacter pylori, is closely associated with the development of gastric cancer. However, we observed that after translocation, CagA is degraded by autophagy and therefore short lived. Autophagy and CagA degradation are induced by the H. pylori vacuolating cytotoxin, VacA, which acted via decreasing intracellular glutathione (GSH) levels, causing reactive oxygen species (ROS) accumulation and Akt activation. Investigating this further, we found that CagA specifically accumulated in gastric cells expressing CD44, a cell-surface marker associated with cancer stem cells. The autophagic pathway in CD44-positive gastric cancer stem-like cells is suppressed because of their resistance to ROS, which is supported by increased intracellular GSH levels. These findings provide a molecular link between H. pylori and gastric carcinogenesis through the specific accumulation of CagA in gastric cancer stem-like cells.

本文言語English
ページ(範囲)764-777
ページ数14
ジャーナルCell Host and Microbe
12
6
DOI
出版ステータスPublished - 13-12-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

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