Bidirectional regulation between TMEFF2 and STAT3 may contribute to Helicobacter pylori-associated gastric carcinogenesis.
The transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is a single-pass transmembrane protein, and it is downregulated in human gastric cancer and levels correlate with tumor progression and time of survival. However, the mechanism of its dysregulation in gastric cancer is little known. Here we investigate its regulatory mechanism and the bidirectional regulation between TMEFF2 and STAT3 in gastric carcinogenesis. TMEFF2 expression was decreased after Helicobacter pylori (H. pylori) infection in vivo and in vitro. STAT3 directly binds to the promoter of TMEFF2 and regulates H. pylori-induced TMEFF2 downregulation in normal gastric GES-1 cells and gastric cancer AGS cells. Conversely, TMEFF2 may suppress the phosphorylation of STAT3 and TMEFF2-induced downregulation of STAT3 phosphorylation may depend on SHP-1. A highly inverse correlation between the expression of TMEFF2 and pSTAT3 was also revealed in gastric tissues. We now show the deregulation mechanism of TMEFF2 in gastric carcinogenesis and identify TMEFF2 as a new target gene of STAT3. The phosphorylation of STAT3 may be negatively regulated by TMEFF2, and the bidirectional regulation between TMEFF2 and STAT3 may contribute to H. pylori-associated gastric carcinogenesis.
['Sun|Tian-Tian|TT|', 'Tang|Jia-Yin|JY|', 'Du|Wan|W|', 'Zhao|Hui-Jun|HJ|', 'Zhao|Gang|G|', 'Yang|Sheng-Li|SL|', 'Chen|Hao-Yan|HY|', 'Hong|Jie|J|', 'Fang|Jing-Yuan|JY|']
D000818:Animals D002471:Cell Transformation, Neoplastic D047369:Chromatin Immunoprecipitation D005753:Gastric Mucosa D015972:Gene Expression Regulation, Neoplastic D005849:Gerbillinae D016481:Helicobacter Infections D016480:Helicobacter pylori D006801:Humans D007124:Immunoenzyme Techniques D008297:Male D008565:Membrane Proteins D009363:Neoplasm Proteins D010766:Phosphorylation D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 D012333:RNA, Messenger D060888:Real-Time Polymerase Chain Reaction D020133:Reverse Transcriptase Polymerase Chain Reaction D050796:STAT3 Transcription Factor D015398:Signal Transduction D013274:Stomach Neoplasms D014407:Tumor Cells, Cultured
TMEFF2 STAT3 gastric cancer H. pylori