Journal of Digestive Cancer Research

Korean Society of Gastrointestinal Cancer Research (대한소화기암연구학회)
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STAT3 and SHP-1: Toward Effective Management of Gastric Cancer

  • Moon Kyung Joo (Division of Gastroenterology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine)
  • Received : 2018.05.10
  • Accepted : 2018.06.19
  • Published : 2018.06.30
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Abstract

The importance of signal transducer and activator of transcription 3 (STAT3) signaling in gastric carcinogenesis was firmly evaluated in the previous studies. Fully activated STAT3 induces various target genes involving tumor invasion and epithelial-mesenchymal transition (EMT), and mediates interaction between cancer cells and microenvironmental immune cells. Thus, suppression of STAT3 activity is an important issue for inhibition of gastric carcinogenesis and invasion. Unfortunately, data from clinical studies of direct inhibitor targeting STAT3 have been disappointing. SH2-containing protein tyrosine phosphatase 1 (SHP-1) effectively dephosphorylates and inhibits STAT3 activity, which has not been extensively studied gastric cancer research field. However, by summarizing recent data, it is evident that protein and gene expression of SHP-1 are minimal in gastric cancer cells, and induction of SHP-1 effectively downregulates phosphorylated STAT3 and inhibits cellular invasion in gastric cancer cells. Several SHP-1 inducers have been investigated in the experimental studies, including proton pump inhibitor, arsenic trioxide, and other natural compounds. Taken together, we suggest that modulation of SHP-1/STAT3 signaling axis may present a new way for treatment of gastric cancer, and development of effective SHP-1 inducer may be an important task in the future search field of gastric cancer.

Keywords

Acknowledgement

This study was financially supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number: NRF-2016R1D1A1A02936964).

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