Helicobacter pylori infected gastric epithelial cells bypass cell death pathway through the oncoprotein Gankyrin

• Published in: Advances in cancer biology - metastasis Vol. 7; p. 100087
• Main Authors: Kashyap, Dharmendra, Varshney, Nidhi, Baral, Budhadev, Kandpal, Meenakshi, Indari, Omkar, Jain, Ajay Kumar, Chatterji, Debi, Kumar, Sachin, Parmar, Hamendra Singh, Sonawane, Avinash, Chandra Jha, Hem
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.07.2023; Elsevier
• Subjects: Autophagy; Cell-signaling; Gankyrin; Helicobacter pylori; Mitochondrial membrane potential; ROS; Cell-signaling; Helicobacter pylori; Gankyrin; Autophagy; ROS; Mitochondrial membrane potential
• ISSN: 2667-3940; 2667-3940
• DOI: 10.1016/j.adcanc.2023.100087

H. pylori infection can lead to gastric diseases by modulating the various cellular processes such as cellular stress, apoptosis, autophagy, and metabolic changes. H. pylori exposed gastric epithelial cells bypass the cell death pathways. However, the underlying molecular mechanisms remain in infancy. Herein, we determined that H. pylori infection on gastric epithelial cells bypass the cell death pathway via the modulation of autophagy-related signaling molecules (LC3B and ATG7) through the host-associated oncoprotein Gankyrin. Upregulated expression of Gankyrin further enhanced the various antioxidant (gclm, gclc, sod2, cat, keap1, ant, and hsf1) and autophagy-associated genes’ transcripts (atg5, atg7, lc3b, beclin, and sqstm1). Elevated expression of Gankyrin also modulates the various downstream signaling proteins such as Akt, Beta-catenin, and NFkB. We also observed altered cancerous properties of gastric epithelial cells viz; apoptosis, wound healing, chemoresistance, biomass and membrane potential of mitochondria. Concisely, the study revealed that H. pylori infection promotes GC via autophagy through the modulation of oncoprotein Gankyrin and cellular reactive oxygen species (ROS). Overall, our study demonstrated the antiapoptotic property of H pylori-infected gastric epithelial cells might govern through Gankyrin-directed autophagy. [Display omitted] •Helicobacter pylori infection bypasses the apoptotic pathway by recruiting Gankyrin-mediated autophagy.•Gankyrin induces cancer properties through the modulation of Akt, Beta-catenin, and NFkB in H. pylori infection.•Gankyrin promotes wound healing properties of gastric epithelial cells.•Knockdown of Gankyrin followed by the treatment of NAC decreases the cancer properties of gastric epithelial cells.