Helicobacter pylori Suppresses Glycogen Synthase Kinase 3β to Promote β-Catenin Activity

Abstract

The human pathogen Helicobacter pylori influences cell adhesion, proliferation, and apoptosis and is involved in gastric adenocarcinoma formation. In our study we analyzed the impact of H. pylori infection on the regulation of ␤-catenin,

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

“…In this sense, evidence has raised the possibility that Wnt/b-catenin pathway plays a role in the pathogenesis of H. pylori infection, including the promotion of pathological changes seen in gastric cancer. Indeed, in vitro H. pylori infection of cells promotes an increase in nuclear levels of b-catenin and TCF/LEF transactivation, with upregulation of the b-catenin target gene cyclin D1 in a CagA-independent manner [220,221] . Among the pleiotropic effects of the vacuolating cytotoxin VacA, Nakayama et al [222] reported that this H. pylori virulence factor induces the Wnt/b-catenin pathway through the activation of the PI3K/Akt signaling pathway.…”

Pleiotropic Actions of Helicobacter pylori Vacuolating Cytotoxin, VacA

“…This multitasking by GSK3β is achieved by its participation in signaling pathways involving the phosphoinositide 3 kinase (PI3K)/ protein kinase B (Akt) cascade. Several studies showed that H. pylori activated the PI3K-Akt signaling pathway in epithelial cells (Sokolova et al 2008;Nakayama et al 2009;Nagy et al 2009;Tabassam et al 2009). Sokolova et al (2008) demonstrated that H. pylori induced inhibition of β -catenin phosphorylation and ubiquitin-dependent degradation, leading to upregulation of T cell factor/lymphoid enhancer-binding factor (Tcf/Lef)-dependent transcription of cyclin D1 by suppression of GSK3β activity.…”

“…Several studies showed that H. pylori activated the PI3K-Akt signaling pathway in epithelial cells (Sokolova et al 2008;Nakayama et al 2009;Nagy et al 2009;Tabassam et al 2009). Sokolova et al (2008) demonstrated that H. pylori induced inhibition of β -catenin phosphorylation and ubiquitin-dependent degradation, leading to upregulation of T cell factor/lymphoid enhancer-binding factor (Tcf/Lef)-dependent transcription of cyclin D1 by suppression of GSK3β activity. In addition, GSK3β inhibition through PI3K-Akt activation by H. pylori resulted in NF-κ B activation and IL-8 production (Tabassam et al 2009).…”

Phosphorylation Regulates NCC Stability and Transporter Activity In Vivo

“…To assess the cell surface stability of WT, T60M, T60A, and T60D HA-NCC in MDCK cells, fresh induction medium supplemented with 20 mg/ml cycloheximide was applied for 1, 2, and 4 hours before harvest of the cells. Whole cell lysate without the nuclear portion prepared as reported previously 54 and membrane fraction prepared with the ProteoExtract native membrane protein extraction kit (Merck-Millipore) 55 were applied for semiquantitative immunoblot. Rat anti-HA mAb (9Y10; Roche Diagnostics), mouse anti-b actin (SC-47778; Sigma), and mouse anti-glyceraldehyde 3-phosphate dehydrogenase (MAB374; Millipore) were used.…”