Fig. 3

CD44 variant-xCT axis-mediated ROS regulation determines the malignant transformation of gastric epithelial cells showing CagA accumulation. Stabilization of xCT (cystine/glutamate antiporter) at the cell membrane in gastric epithelial stem cells due to high CD44v8-10 expression promotes glutathione synthesis, thereby inactivating the Akt signaling pathway. Phosphorylated Akt in CD44v-negative cells induces ubiquitin-proteasome-dependent degradation of p53 in the cytoplasm. Activated Akt signal transduction in non-cancer stem-like cells expressing the standard isoform of CD44 exhibit selective autophagy-mediated degradation of CagA. CagA is translocated from H. pylori via type IV secretion channels, and importantly, accumulation of this pathogenic protein in CD44v-expressing cancer stem-like cells leads to carcinogenesis and maintenance of “stemness.” Note that the red bar shows the relatively high level, while the blue bar indicates the low level