Helicobacter pylori-controlled c-Abl localization promotes cell migration and limits apoptosis

Area of Science:

• Oncology
• Microbiology
• Cell Biology

Background:

• Deregulated c-Abl tyrosine kinase activity is implicated in various cancers.
• Helicobacter pylori (Hp) activates c-Abl, phosphorylating oncoprotein CagA, but CagA-independent roles are less understood.

Purpose of the Study:

• Investigate c-Abl activity and localization in gastric H. pylori pathogenesis.
• Elucidate c-Abl's role in both CagA-dependent and -independent pathways.

Main Methods:

• Analyzed c-Abl phosphorylation and localization via immunostaining and immunofluorescence.
• Identified interaction partners using tandem-affinity purification and assessed cell behavior (elongation, migration, apoptosis).
• Investigated c-Abl's role in H. pylori pathogenesis in mouse models and human biopsies.

Main Results:

• Identified a novel mechanism where H. pylori's type-IV secretion system effector βHBP and PKC induce c-Abl threonine 735 phosphorylation (pAbl^T735).
• pAbl^T735 interacts with 14-3-3 proteins, causing cytoplasmic retention and potentiating H. pylori-mediated cell elongation and migration.
• Nuclear exclusion of pAbl^T735 attenuated apoptosis, and enhanced c-Abl/pAbl^T735 levels were observed in human H. pylori gastritis patients.

Conclusions:

• H. pylori infection hijacks c-Abl, altering its subcellular localization to promote epithelial-mesenchymal transition-like processes.
• This novel regulatory mechanism contributes to H. pylori pathogenesis by enhancing cell migration and inhibiting apoptosis.