Autophagy mediates ER stress and inflammation in -related gastric cancer. Mommersteeg M C,Simovic I,Yu B,van Nieuwenburg S A V,Bruno I M J,Doukas M,Kuipers E J,Spaander M C W,Peppelenbosch M P,Castaño-Rodríguez N,Fuhler G M Gut microbes Autophagy is a cellular degradation mechanism, which is triggered by the bacterium . A single nucleotide polymorphism (SNP) in the autophagy gene (rs2241880, G-allele) has been shown to dysregulate autophagy and increase intestinal endoplasmic reticulum (ER) stress. Here, we investigate the role of this SNP in -mediated gastric carcinogenesis and its molecular pathways. rs2241880 was genotyped in subjects from different ethnic cohorts (Dutch and Australian) presenting with gastric (pre)malignant lesions of various severity. Expression of GRP78 (a marker for ER stress) was assessed in gastric tissues. The effect of rs2241880 on -mediated ER stress and pro-inflammatory cytokine induction was investigated in organoids and CRISPR/Cas9 modified cell lines. Development of gastric cancer was associated with the rs2241880 G-allele. Intestinal metaplastic cells in gastric tissue of patients showed increased levels of ER-stress. models showed that increases autophagy while reducing ER stress, which appeared partly mediated by the rs2241880 genotype. -induced IL-8 production was increased while TNF-α production was decreased, in cells homozygous for the G-allele. The rs2241880 G-allele is associated with progression of gastric premalignant lesions and cancer. Modulation of -induced ER stress pathways and pro-inflammatory mediators by rs2441880 may underlie this increased risk. 10.1080/19490976.2021.2015238

Helicobacter pylori infection promotes autophagy through Nrf2-mediated heme oxygenase upregulation in human gastric cancer cells. Paik Ji Yeon,Lee Hee Geum,Piao Juan-Yu,Kim Su-Jung,Kim Do-Hee,Na Hye-Kyung,Surh Young-Joon Biochemical pharmacology It has been reported that Helicobacter pylori (H. pylori) infection is one of the primary causes of gastritis and peptic ulcer diseases. More than 50% of the world's population is supposed to be infected by this bacterium. However, 90% of infected patients do not develop gastric cancer, suggesting the existence of host defence mechanisms. Nrf2 is a transcription factor that plays a key role in cellular defence against oxidative stress and inflammation. Autophagy, an autodigestive process that degrades cellular organelles and proteins, plays an important role in maintaining cellular homeostasis. To investigate the molecular mechanisms responsible for cellular adaptive response to H. pylori induced gastric inflammation, human gastric epithelial cells and mice were infected with H. pylori. H. pylori infection induced expression of microtubule-associated light chain3 (LC3), an autophagic marker, through accumulation of reactive oxygen species and subsequently nuclear translocation of the redox-sensitive transcription factor, Nrf2 in human gastric epithelial AGS cells. Furthermore, Nrf2-induced LC3 up-regulation was mediated by heme oxygenase-1 (HO-1) and its by-product, carbon monoxide. Taken together, the Nrf2-HO-1 axis is considered to play a role in cellular adaptive survival response to H. pylori-induced gactric carcinogenesis by inducing autophagy. 10.1016/j.bcp.2019.02.003