No abstract

H. pylori induce ETS2 and Twist1 expression in the infected GCC.ETS2 and Twist1 transcriptionally activate siah2 in the H. pylori-infected GCCs.H. pylori-mediated Siah2 induction enhances motility and invasiveness of the infected GCCs.

Tumor masses are deprived of oxygen and characterized by enhanced glucose uptake followed by glycolysis. Elevated glucose levels induce non-enzymatic glycosylation or glycation of proteins which leads to accumulation of advanced glycation end products (AGE). These AGE molecules bind to their respective receptors called the receptor for advanced glycation end products (RAGE) and initiate several aberrant signaling pathways leading to onset of diseases such as diabetes, Alzheimer's, atherosclerosis, heart failure and cancer. The role of AGE in cancer progression is being extensively studied in recent years. As cancer cells are hypoxic in nature and adapted to glycolysis, which induces glycation, its effects need to be understood in greater detail. Since AGE-RAGE signaling is involved in cancer progression, inhibition of AGE-RAGE interaction could be a potential therapeutic target. The purpose of this review is to highlight the role of AGE-RAGE interaction in hypoxic cancer cells.

Helicobacter pylori induces the antiapoptotic protein myeloid cell leukemia 1 (Mcl1) in human gastric epithelial cells (GECs). Apoptosis of oncogenic protein Mcl1‐expressing cells is mainly regulated by Noxa‐mediated degradation of Mcl1. We wanted to elucidate the status of Noxa in H. pylori‐infected GECs. For this, various GECs such as AGS, MKN45, and KATO III were either infected with H. pylori or left uninfected. The effect of infection was examined by immunoblotting, immunoprecipitation, chromatin immunoprecipitation assay, in vitro binding assay, flow cytometry, and confocal microscopy. Infected GECs, surgical samples collected from patients with gastric adenocarcinoma as well as biopsy samples from patients infected with H. pylori showed significant up‐regulation of both Mcl1 and Noxa compared with noninfected samples. Coexistence of Mcl1 and Noxa was indicative of an impaired Mcl‐Noxa interaction. We proved that Noxa was phosphorylated at Ser13 residue by JNK in infected GECs, which caused cytoplasmic retention of Noxa. JNK inhibition enhanced Mcl1‐Noxa interaction in the mitochondrial fraction of infected cells, whereas overexpression of nonphosphorylatable Noxa resulted in enhanced mitochondria‐mediated apoptosis in the infected epithelium. Because phosphorylation‐dephosphorylation can regulate the apoptotic function of Noxa, this could be a potential target molecule for future treatment approaches for H. pylori‐induced gastric cancer.—Rath, S., Das, L., Kokate, S. B., Pratheek, B. M., Chattopadhyay, S., Goswami, C., Chattopadhyay, R., Crowe, S. E., Bhattacharyya, A., Regulation of Noxa‐mediated apoptosis in Helicobacter pylori–infected gastric epithelial cells. FASEB J. 29, 796–806 (2015). http://www.fasebj.org