4.6 Article

TNF-α-inducing protein of Helicobacter pylori induces epithelialmesenchymal transition (EMT) in gastric cancer cells through activation of IL-6/STAT3 signaling pathway

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.01.110

Keywords

Helicobacter pylori; TNF-alpha inducing protein (Tip alpha); IL-6/STAT3 pathway; Gastric cancer; Epithelial-mesenchymal transition (EMT)

Funding

  1. Construct Program of the Key Discipline in Hunan Province [2011-75]
  2. Hunan Provincial Key Laboratory for Special Pathogen Prevention and Control Foundation [2014-5]
  3. Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study [2015-351]
  4. Research Project of Hunan Provincial Education Department [16K078]

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Tumor necrosis factor (TNF)-alpha-inducing protein (Tip alpha) is a newly identified carcinogenic factor secreted by Helicobacter pylori (H.pylori). Although it has been proved that Tipa is a strong inducer of epithelialmesenchymal transition (EMT), a crucial process of migration, the exact molecular mechanism is unknown. Current evidence indicates that the oncogenic transcription factor signal transducers and activators of transcription 3 (STAT3) is inappropriately activated in multiple malignancies, including gastric cancer. In this study, we showed that Tipa significantly down-regulated the expression of EMT-related markers E-cadherin as well as up-regulated N-cadherin and vimentin in SGC7901 cells, with typical morphological changes of EMT. Tipa also promoted proliferation and migration of SGC7901 cells. Furthermore, Tipa activated interleukin-6 (IL-6)/STAT3 signaling pathway in SGC7901 cells. The effects of Tipa treatment observed was abolished when we block IL-6/STAT3 signaling pathway. Altogether, our data demonstrated that Tipa may accelerate tumor aggressiveness in gastric cancer by promoting EMT through activation of IL-6/STAT3 pathway. (C) 2017 Elsevier Inc. All rights reserved.

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