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

Wandler, Anica M.; Guillemin, Karen

doi:10.1371/journal.ppat.1002939

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

Journal Article · Thu Oct 18 04:00:00 EDT 2012 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1002939· OSTI ID:1627906

Wandler, Anica M. ^[1]; Guillemin, Karen ^[2]

University of Oregon, Eugene, OR (United States); DOE/OSTI
University of Oregon, Eugene, OR (United States)

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.

Research Organization:: University of Oregon, Eugene, OR (United States)

Sponsoring Organization:: National Institutes of Health (NIH); Rosaria Haugland Graduate Research Fellowship in Chemistry

OSTI ID:: 1627906

Journal Information:: PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 10 Vol. 8; ISSN 1553-7374

Publisher:: Public Library of Science

Country of Publication:: United States

Language:: English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
apoptosis
c-Jun N-terminal kinase signaling cascade
drosophila melanogaster
epithelium
gastric cancer
helicobacter pylori
imaginal discs
phenotypes

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

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Cited By (11)

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