title: Helicobacter pylori promotes epithelial-mesenchymal transition in gastric cancer by downregulating programmed cell death protein 4 (PDCD4).
abstract: Helicobacter pylori, a Gram-negative, microaerophilic bacterium found in the stomach, is assumed to be associated with carcinogenesis, invasion and metastasis in digestive diseases. Cytotoxin-associated gene A (CagA) is an oncogenic protein of H. pylori that is encoded by a Cag pathogenicity island related to the development of gastric cancer. The epithelial-mesenchymal transition (EMT) is the main biological event in invasion or metastasis of epithelial cells. H. pylori may promote EMT in human gastric cancer cell lines, but the specific mechanisms are still obscure. We explored the underlying molecular mechanism of EMT induced by H. pylori CagA in gastric cancer. In our article, we detected gastric cancer specimens and adjacent non-cancerous specimens by immunohistochemistry and found increased expression of the EMT-related regulatory protein TWIST1 and the mesenchymal marker vimentin in cancer tissues, while programmed cell death factor 4 (PDCD4) and the epithelial marker E-cadherin expression decreased in cancer specimens. These changes were associated with degree of tissue malignancy. In addition, PDCD4 and TWIST1 levels were related. In gastric cancer cells cocultured with CagA expression plasmid, CagA activated TWIST1 and vimentin expression, and inhibited E-cadherin expression by downregulating PDCD4. CagA also promoted mobility of gastric cancer cells by regulating PDCD4. Thus, H. pylori CagA induced EMT in gastric cancer cells, which reveals a new signaling pathway of EMT in gastric cancer cell lines.
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China; Departments of Biochemistry, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Jiping
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Xiuming
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Wenfu
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Yundong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Shili
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Jia
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015870:Gene Expression; D016480:Helicobacter pylori / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D015820:Cadherins; D009687:Nuclear Proteins; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D014746:Vimentin; C080866:cagA protein, Helicobacter pylori