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

被引:32
|
作者
Wandler, Anica M. [1 ]
Guillemin, Karen [1 ]
机构
[1] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA
基金
美国国家卫生研究院;
关键词
GASTRIC-CANCER; EPITHELIAL POLARITY; ONCOGENIC RAS; TUMOR-GROWTH; CELL; MOTILITY; KINASE;
D O I
10.1371/journal.ppat.1002939
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
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.
引用
收藏
页数:14
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