The Role of Gastrokine 1 in Gastric Cancer.
10.5230/jgc.2014.14.3.147
- Author:
Jung Hwan YOON
1
;
Won Suk CHOI
;
Olga KIM
;
Won Sang PARK
Author Information
1. Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea. wonsang@catholic.ac.kr
- Publication Type:Review
- Keywords:
GKN1 protein;
Homeostasis;
Gastritis;
Stomach neoplasms;
Tumor suppressor gene
- MeSH:
Apoptosis;
Cell Cycle;
Cell Proliferation;
Cell Survival;
Cyclooxygenase 2;
Epigenomics;
Gastric Mucosa;
Gastritis;
Genes, Tumor Suppressor;
Helicobacter pylori;
Homeostasis;
Inflammation;
Metaplasia;
Neoplasm Metastasis;
Reactive Oxygen Species;
Stomach;
Stomach Neoplasms*
- From:Journal of Gastric Cancer
2014;14(3):147-155
- CountryRepublic of Korea
- Language:English
-
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-kappaB 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 gastric-specific 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.
