GKN1 inhibits cell invasion in gastric cancer by inactivating the NF-kappaB pathway.
Metastasis is a relatively early event and a major cause of death in gastric cancer (GC) patients. Gastrokine 1 (GKN1) is a stomach-specific protein that is normally expressed in gastric mucosa but not in primary tumors or cell lines. We and others have demonstrated that GKN1 inhibits cell growth; however, its role in metastasis is not clear. In this study, we explored the role of GKN1 in cell invasion. Immunohistochemistry (IHC) was used to measure the expression of GKN1 in precancerous lesions and in GCs. The cell invasion assay was employed to examine the effect of GKN1 on cell invasion. The molecular mechanism of GKN1 in inhibiting GC cell invasion in vitro was explored by western blotting. We noted a gradual decrease in GKN1 expression from normal mucosa to dysplastic gastric tissue to GC, and that low GKN1 expression was associated with metastasis (P=0.003). We showed that GKN1 inhibits cell invasion by downregulating MMP2 expression through the NF-κB pathway. These results provide molecular evidence that GKN1 inhibits metastasis in GC cells, and indicate that GKN1 is a potential novel therapeutic target for gastric cancer.
Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Rui
R
Xing
Jian-Tao
JT
Cui
Nan
N
Xia
You-Yong
YY
Lu
D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D036361:Peptide Hormones / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
C477000:GKN1 protein, human; D016328:NF-kappa B; D036361:Peptide Hormones; D020778:Matrix Metalloproteinase 2