title: Gastrin promotes the metastasis of gastric carcinoma through the β-catenin/TCF-4 pathway.
abstract: Gastric cancer is the most common epithelial malignancy and the second leading cause of cancer-related death worldwide; metastasis is a crucial factor in the progression of gastric cancer. The present study applied gastrin-17 amide (G-17) in SGC7901 cells. The results showed that G-17 promoted the cell cycle by accelerating the G0/G1 phase and by increasing the cell proliferation rate by binding to the gastrin receptor. The migratory and invasive abilities of the SGC7901 cells were increased by G-17. The expression levels of matrix metalloproteinase (MMP)-7, MMP-9 and vascular endothelial growth factor (VEGF) were enhanced by G-17 as well. Moreover, G-17 caused the overexpression of β-catenin and TCF-4. G-17 also caused a preferential cytoplasmic and nuclear localization of β-catenin with a high TOP-FLASH activity. Finally, axin reduced the migratory and invasive abilities of the SGC7901 cells, and inhibited the expression of β-catenin, TCF-4, MMP-7, MMP-9 and VEGF; these effects were counteracted by adding G-17. In summary, the present study confirmed the proliferation and metastasis-promoting role of G-17 via binding to the gastrin receptor, and the β-catenin/TCF-4 pathway was found to be essential for mediating G-17-induced metastasis in gastric cancer. These results may provide a novel gene target for the treatment of gastric cancer.
authors.affiliation: Division of Gastroenterology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710003, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhuang
authors.affiliation: Division of Gastroenterology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710003, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Division of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710003, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, P.R. China.
authors.forename: Lingxia
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Han
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D005755:Gastrins / Q000009:adverse effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology*; D043887:Receptor, Cholecystokinin B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005755:Gastrins; D043887:Receptor, Cholecystokinin B; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; C013550:gastrin 17; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9