Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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The Role of Gastrokine 1 in Gastric Cancer

  • Yoon, Jung Hwan (Department of Pathology, College of Medicine, The Catholic University of Korea) ;
  • Choi, Won Suk (Department of Pathology, College of Medicine, The Catholic University of Korea) ;
  • Kim, Olga (Department of Pathology, College of Medicine, The Catholic University of Korea) ;
  • Park, Won Sang (Department of Pathology, College of Medicine, The Catholic University of Korea)
  • Received : 2014.08.12
  • Accepted : 2014.09.13
  • Published : 2014.09.30
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Abstract

Homeostatic imbalance between cell proliferation and death in gastric mucosal epithelia may lead to gastritis and gastric cancer. Despite abundant gastrokine 1 (GKN1) expression in the normal stomach, the loss of GKN1 expression is frequently detected in gastric mucosa infected with Helicobacter pylori, as well as in intestinal metaplasia and gastric cancer tissues, suggesting that GKN1 plays an important role in gastric mucosal defense, and the gene functions as a gastric tumor suppressor. In the stomach, GKN1 is involved in gastric mucosal inflammation by regulating cytokine production, the nuclear factor-${\kappa}B$ signaling pathway, and cyclooxygenase-2 expression. GKN1 also inhibits the carcinogenic potential of H. pylori protein CagA by binding to it, and up-regulates antioxidant enzymes. In addition, GKN1 reduces cell viability, proliferation, and colony formation by inhibiting cell cycle progression and epigenetic modification by down-regulating the expression levels of DNMT1 and EZH2, and DNMT1 activity, and inducing apoptosis through the death receptor-dependent pathway. Furthermore, GKN1 also inhibits gastric cancer cell invasion and metastasis via coordinated regulation of epithelial mesenchymal transition-related protein expression, reactive oxygen species production, and PI3K/Akt signaling pathway activation. Although the modes of action of GKN1 have not been clearly described, recent limited evidence suggests that GKN1 acts as a gastricspecific tumor suppressor. This review aims to discuss, comment, and summarize the recent progress in the understanding of the role of GKN1 in gastric cancer development and progression.

Keywords

References

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