Helicobacter pylori CagA Suppresses Apoptosis through Activation of AKT in a Nontransformed Epithelial Cell Model of Glandular Acini Formation

• Published in: BioMed research international Vol. 2015; no. 2015; pp. 1 - 12
• Main Authors: Fuentes-Pananá, Ezequiel M., Legorreta-Haquet, Maria Victoria, Torres-Morales, Julián, Camorlinga-Ponce, Margarita, Meza, Isaura, Arévalo-Romero, Haruki, Sandoval-Montes, Claudia, Torres, Javier, Vallejo-Flores, Gabriela, Chávez-Rueda, Adriana Karina
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01-01-2015; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Acinar Cells; Antigens, Bacterial - metabolism; Antigens, Bacterial - pharmacology; Apoptosis; Apoptosis - drug effects; Bacterial Proteins - metabolism; Bacterial Proteins - pharmacology; Cancer; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Deoxyribonucleic acid; DNA; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - drug effects; Grants; Health aspects; Helicobacter Infections - microbiology; Helicobacter pylori; Helicobacter pylori - pathogenicity; Host-bacteria relationships; Humans; Immunology; Kinases; Models, Biological; Observations; Pathogenesis; Phosphorylation; Phosphotransferases; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rodents; Studies; Transgenic animals; Ulcers
• DOI: 10.1155/2015/761501
• EISSN: 2314-6141
• ISSN: 2314-6133

H. pylori infection is the most important environmental risk to develop gastric cancer, mainly through its virulence factor CagA. In vitro models of CagA function have demonstrated a phosphoprotein activity targeting multiple cellular signaling pathways, while cagA transgenic mice develop carcinomas of the gastrointestinal tract, supporting oncogenic functions. However, it is still not completely clear how CagA alters cellular processes associated with carcinogenic events. In this study, we evaluated the capacity of H. pylori CagA positive and negative strains to alter nontransformed MCF-10A glandular acini formation. We found that CagA positive strains inhibited lumen formation arguing for an evasion of apoptosis activity of central acini cells. In agreement, CagA positive strains induced a cell survival activity that correlated with phosphorylation of AKT and of proapoptotic proteins BIM and BAD. Anoikis is a specific type of apoptosis characterized by AKT and BIM activation and it is the mechanism responsible for lumen formation of MCF-10A acini in vitro and mammary glands in vivo. Anoikis resistance is also a common mechanism of invading tumor cells. Our data support that CagA positive strains signaling function targets the AKT and BIM signaling pathway and this could contribute to its oncogenic activity through anoikis evasion.