Helicobacter pylori-induced STAT3 activation and signalling network in gastric cancer
Junhong Zhao1,*, Yujuan Dong1,3,*, Wei Kang 2, Minnie Y. Go1, Joanna HM. Tong2, Enders KW. Ng3, Philip WY. Chiu3, Alfred SL. Cheng1, Ka Fai To2, Joseph JY. Sung1, Jun Yu1
1 Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
2 Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China
3 Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
* The authors contribute equally to this study.
Correspondence:
Jun Yu, email:
Keywords: Helicobacter pylori; STAT3; gastric carcinogenesis; molecular regulator
Received: June 25, 2014 Accepted: July 2, 2014 Published: July 3, 2014
Abstract
Background: Helicobacter pylori (H. pylori) is the most important gastric carcinogen. However, the mechanisms of H. pylori induced gastric carcinogenesis through STAT3 activation are largely unknown. We evaluated the effects of H. pylori infection on STAT3 activation and dissected the signalling network of STAT3 in H. pylori-infected gastric carcinogenesis.
Methods: The expression of phospho-STAT3 (pSTAT3) was evaluated by immunohistochemistry and western blot. Gene expression array and chromatin immunoprecipitation were used to dissect the STAT3 signalling network on H. pylori co-cultured AGS.
Results: pSTAT3 was significantly higher in H. pylori-positive gastritis than in H. pylori-negative gastritis (P = 0.003). In addition, 98% of H. pylori positive intestinal metaplasia specimens showed STAT3 activation, whereas pSTAT3 was significantly decreased in all 43 specimens one year after H. pylori eradication (P < 0.001). Moreover, pSTAT3 was only detected in the H. pylori-infected gastric tissues of mice but not in control mice. We further identified 6 candidates (BRUNOL4, FGFR1, SHOX2, JAK3, MAPK8, and PDPN) were directly up-regulated by H. pylori induced STAT3 activation.
Conclusion: H. pylori infection triggers the activation of STAT3 and de-regulates multitude of tumorigenic genes which may contribute to the initiation and progression of gastric cancer.
