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

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)764-777
Number of pages14
JournalCell Host and Microbe
Volume12
Issue number6
DOIs
Publication statusPublished - 2012 Dec 13

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Neoplastic Stem Cells
Helicobacter pylori
Stomach Neoplasms
Reactive Oxygen Species
Autophagy
Stomach
Glutathione
Carcinogenesis

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Cancer Research
  • Molecular Biology

Cite this

Reactive oxygen species-induced autophagic degradation of helicobacter pylori CagA is specifically suppressed in cancer stem-like cells. / Tsugawa, Hitoshi; Suzuki, Hidekazu; Saya, Hideyuki; Hatakeyama, Masanori; Hirayama, Toshiya; Hirata, Kenro; Nagano, Osamu; Matsuzaki, Juntaro; Hibi, Toshifumi.

In: Cell Host and Microbe, Vol. 12, No. 6, 13.12.2012, p. 764-777.

Research output: Contribution to journalArticle

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AU - Hirata, Kenro

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AU - Matsuzaki, Juntaro

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