title: Helicobacter pylori-induced alteration of epithelial cell signaling and polarity: a possible mechanism of gastric carcinoma etiology and disparity.
abstract: Gastric cancer, a disease of disparity associated with Helicobacter pylori (H. pylori) infection, is the world's second leading cause of cancer deaths. The pathogen H. pylori target the epithelial adhesion receptors, E-cadherin, and β1-integrin, to modulate the host cytoskeleton via disruption of the epithelial cell polarity necessary for maintaining the infection, but how this leads to the development of the carcinoma is widely unclear. While Rho family GTPases' signaling to the cytoskeleton and these receptors is required for initiating and maintaining the infection, the responsible effectors, and how they might influence the etiology of the carcinomas are currently unknown. Here we discuss the potential role of the Cdc42-IQGAP1 axis, a negative regulator of the tumor suppressors E-cadherin and β1-integrin, as a potential driver of H. pylori-induced gastric carcinoma and propose avenues for addressing its disparity. Chronic dysfunction of the IQGAP1-signaling pathway, resulting from H. pylori-induced disruption of cell polarity, can explain the pathogenesis of the carcinoma, at least, in subsets of infected population, and thus could provide a potential means for personalized medicine.
authors: Department of Molecular Pharmacology, Physiology and Biotechnology, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA. mahasin_osman@Brown.edu
authors: Mahasin A
authors: MA
authors: Osman
authors: George S
authors: GS
authors: Bloom
authors: Emmanuel A
authors: EA
authors: Tagoe
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000382:microbiology* / Q000473:pathology*; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology*
keywords: Akt; Cdc42; Erk1/2; H. pylori; IQGAP; gastric cancer; mTOR
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