Helicobacter pylori infection induced gastric cancer; advance in gastric stem cell research and the remaining challenges

Helicobacter pylori, a microaerophilic, spiral-shaped Gram-negative bacterium, colonized in human stomach, is the major cause of chronic gastritis, peptic ulcers, and gastric malignancies, including gastric non-cardia adenocarcinoma and mucosal-associated lymphoid tissue (MALT) lymphoma [1]. Epidemiologically, H. pylori infects half of the world’s population, although most infected persons have no clinical presentation, approximately 1% infected people will develop into gastric cancer [2]. Despite ample amount of efforts in investigating its pathogenesis and host-pathogen interactions, the molecular mechanisms of how H. pylori infection induces gastric cancer remain poorly understood.Gastric cancer (GC) is the second leading cause of cancer related death among all cancers, next only to lung cancer. Although the relationship between H. pylori infection and gastric cancer has been very well established, the mechanisms of how tumor initiation and the early development remain elusive. Studies in past decades have suggested that stem cells play a pivotal role in the initiation of gastric cancers, and the tumor can originate from bone marrow derived cells [3]. However, it is not clear how they give rise to tumors after inflammatory insult or bacterial infection; in this work, we briefly discuss the current progress and important challenges for future research.Four major virulence factors have been identified from H. pylori (Table 1), including cytotoxin-associated antigen A (CagA), cag-pathogenicity island (cagPAI), vacuolating cytotoxin (VacA), and outer membrane proteins (OMPs). H. pylori cagPAI is a 40 kilobase region of H. pylori genome that encodes about 30 genes, some of them encode type four secretion system (TFSS), which are essential for pathogenesis and are responsible for delivery of CagA protein and peptidoglycan (PGN) into host cells [4,5]. H. pylori CagA is encoded by cagA gene within the cagPAI, has a molecular weight around 120–145 kDa, induces multiple ho