Transgenic Expression of the Helicobacter pylori Virulence Factor CagA Promotes Apoptosis or Tumorigenesis through JNK Activation in Drosophila

PLoS Pathogens

Anica M. Wandler¹ 

[1] Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America

关键词: Apoptosis;    c-Jun N-terminal kinase signaling cascade;    Imaginal discs;    Epithelium;    Phenotypes;    Helicobacter pylori;    Drosophila melanogaster;    Cell polarity;   

DOI  :  10.1371/journal.ppat.1002939

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Gastric cancer development is strongly correlated with infection by Helicobacter pylori possessing the effector protein CagA. Using a transgenic Drosophila melanogaster model, we show that CagA expression in the simple model epithelium of the larval wing imaginal disc causes dramatic tissue perturbations and apoptosis when CagA-expressing and non-expressing cells are juxtaposed. This cell death phenotype occurs through activation of JNK signaling and is enhanced by loss of the neoplastic tumor suppressors in CagA-expressing cells or loss of the TNF homolog Eiger in wild type neighboring cells. We further explored the effects of CagA-mediated JNK pathway activation on an epithelium in the context of oncogenic Ras activation, using a Drosophila model of metastasis. In this model, CagA expression in epithelial cells enhances the growth and invasion of tumors in a JNK-dependent manner. These data suggest a potential role for CagA-mediated JNK pathway activation in promoting gastric cancer progression.

【 授权许可】

CC BY