Helicobacter pylori cancer associated CagA protein drives intestinal metaplastic transition in human gastric organoids
Reines, M.; Soerensen, M.; Berger, H.; Schlaermann, P.; Patel, M.; Meyer, T. F.
Show abstract
Gastric intestinal metaplasia (GIM) constitutes a pre-neoplastic stage in the development of stomach cancer. While strong evidence points to a role of infection with CagA positive Helicobacter pylori in the development of GIM, currently available experimental models have not provided mechanistic clues on this association. Here, we ectopically expressed the H. pylori CagA protein in human gastric organoids derived from normal, primary epithelial cells. Native CagA protein was produced and rapidly processed to yield a tyrosine-phosphorylated C-terminal fragment of [~]35 kDa. It led to an activation of the STAT3 pathway and aberrant elevation of CDX2 expression, a marker of intestinal type of cells, as well as other intestinal markers. Thus, CagA drives re-programming of gastric cells towards an intestinal-like phenotype, towards GIM. In summary, we describe a cooperative mechanism of CagA-induced STAT3 signaling and intestinal-like trans-differentiation, promoting a pre-neoplastic state. Our model provides mechanistic evidence for a direct role of CagA in driving premalignancy in gastric pathogenesis.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- An iPSC-derived small intestine-on-chip with self-organizing epithelial, mesenchymal and neural cells 95%
- Disruptions in cell fate decisions and transformed enteroendocrine cells drive intestinal tumorigenesis in Drosophila. 94%
- PI5P4Kα Regulates Iron Balance to Promote Metabolic Fitness in Pancreatic Cancer 94%
Similar papers in this journal
- Tofacitinib uptake by patient-derived intestinal organoids predicts individual clinical responsiveness 95%
- Single nucleus and in situ RNA sequencing reveals cell topographies in the human pancreas 94%
- Intestinal Bacteria Maintain Adult Enteric Nervous System and Nitrinergic Neurons via Toll-like Receptor 2-induced Neurogenesis in Mice 94%
Similar papers in this journal
- The Stmn1-lineage contributes to acinar regeneration but not to neoplasia upon oncogenic Kras expression 94%
- Enteroendocrine cells protect the stem cell niche by regulating crypt metabolism in response to nutrients 94%
- A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics 94%
Similar papers in this journal
- Microbial stimulation of oxytocin release from the intestinal epithelium via secretin signaling 95%
- Blood-borne immune cells carry low biomass DNA remnants of microbes in patients with colorectal cancer or inflammatory bowel disease 92%
- Gut microbiome shifts in adolescents after sleeve gastrectomy with increased oral-associated taxa and pro-inflammatory potential 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.