Sougleri et al., 2016. Helicobacter pylori CagA protein induces factors involved in the epithelial to mesenchymal transition (EMT) in infected gastric epithelial cells in an EPIYA- phosphorylation-dependent manner. FEBS J. 283(2), 206-220. PMID-26907789; Full Text: Wiley (Download PDF)
This research article investigates how the CagA effector protein of Helicobacter pylori contributes to cancer-associated cellular changes, specifically epithelial to mesenchymal transition (EMT). This study provides strong evidence that CagA-induced EMT is mediated by phosphorylation of its EPIYA motifs, linking H. pylori infection to gastric carcinogenesis via modulation of host cell signaling and phenotype.
Key Findings:
- The study demonstrates that H. pylori infection leads to the induction of EMT markers in gastric epithelial cells. EMT is a process where epithelial cells lose their characteristics (like cell-cell adhesion) and gain mesenchymal features (like motility), contributing to cancer progression and metastasis.
- The EMT-inducing activity of CagA depends on its EPIYA motifs. These motifs are phosphorylated by host kinases and are critical for CagA’s interaction with various host cell signaling proteins.
- Mutant CagA proteins lacking phosphorylatable EPIYA motifs showed a significantly reduced ability to induce EMT-related changes. This confirms that tyrosine phosphorylation of EPIYA motifs is required for EMT induction.
- Upon infection with H. pylori expressing functional CagA, there was an upregulation of key EMT transcription factors such as Snail1, Slug, and ZEB1, and a downregulation of epithelial markers like E-cadherin.
- Infected cells also exhibited morphological changes typical of EMT, including loss of cell-cell contact and a more spindle-like, fibroblastic appearance.
