title: Helicobacter pylori virulence factor CagA promotes tumorigenesis of gastric cancer via multiple signaling pathways.
abstract: Helicobacter pylori (H. pylori) infection is strongly associated with the development of gastric diseases but also with several extragastric diseases. The clinical outcomes caused by H. pylori infection are considered to be associated with a complex combination of host susceptibility, environmental factors and bacterial isolates. Infections involving H. pylori strains that possess the virulence factor CagA have a worse clinical outcome than those involving CagA-negative strains. It is remarkable that CagA-positive H. pylori increase the risk for gastric cancer over the risk associated with H. pylori infection alone. CagA behaves as a bacterial oncoprotein playing a key role in H. pylori-induced gastric cancer. Activation of oncogenic signaling pathways and inactivation of tumor suppressor pathways are two crucial events in the development of gastric cancer. CagA shows the ability to affect the expression or function of vital protein in oncogenic or tumor suppressor signaling pathways via several molecular mechanisms, such as direct binding or interaction, phosphorylation of vital signaling proteins and methylation of tumor suppressor genes. As a result, CagA continuously dysregulates of these signaling pathways and promotes tumorigenesis. Recent research has enriched our understanding of how CagA effects on these signaling pathways. This review summarizes the results of the most relevant studies, discusses the complex molecular mechanism involved and attempts to delineate the entire signaling pathway.
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China. yongx86@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Yong
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China. 523884584@qq.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China. 934264@qq.com.
authors.forename: Bo-Sheng
authors.initials: BS
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China. 153673804@qq.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China. 416341723@qq.com.
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China. 330295124@qq.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China. 749296838@qq.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China. h2dong@ucsd.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, P.R. China. shimingyang@yahoo.com.
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Yang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013270:Stomach / Q000382:microbiology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D016159:Tumor Suppressor Protein p53; D037521:Virulence Factors; C080866:cagA protein, Helicobacter pylori