Reactive oxygen species-induced autophagic degradation of Helicobacter pylori CagA is specifically suppressed in cancer stem-like cells.
Cell Host Microbe
; 12(6): 764-77, 2012 Dec 13.
Article
en En
| MEDLINE
| ID: mdl-23245321
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Proteínas Bacterianas
/
Helicobacter pylori
/
Especies Reactivas de Oxígeno
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Factores de Virulencia
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Antígenos Bacterianos
Límite:
Humans
Idioma:
En
Revista:
Cell Host Microbe
Asunto de la revista:
MICROBIOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos