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KMID : 1140220210260020137
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대한암예방학회지
2021 Volume.26 No. 2 p.137 ~ p.144
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Trefoil Factor 1 Suppresses Epithelial-mesenchymal Transition through Inhibition of TGF-beta Signaling in Gastric Cancer Cells
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Lee Da-Young
Song Moon-Young
Kim Eun-Hee
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Abstract
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Gastric cancer is a malignancy with high incidence and mortality worldwide. In gastric cancer, epithelial-mesenchymal transition (EMT) and metastasis further increase the mortality rate. Trefoil factor 1 (TFF1) has been reported as a protective factor in the gastric mucosa. In this study, TFF1 inhibited the migration and invasive capability of gastric cancer cells. Elevated TFF1 levels induced the expression of E-cadherin, the epithelial marker, and reduced the expression of N-cadherin, vimentin, Snail, Twist, Zinc finger E-box binding homeobox (ZEB) 1 and ZEB2, well-known repressors of E-cadherin expression. In addition, the expression of matrix metalloproteinase (MMP)-2, MMP-7 and MMP-9, which are major markers of cancer metastasis, was suppressed by TFF1. Up-regulation of TFF1 inhibited TGF-β, a major signaling for EMT induction, and the phosphorylation of Smad2/3 activated by TGF-β in AGS cells. In conclusion, TFF1 inhibits EMT through suppression of TGF-β signaling in AGS cells, which might be used in therapeutic strategies for reducing metastatic potential and invasiveness of these cells.
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KEYWORD
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Gastric cancer, Trefoil factor 1, Epithelial-mesenchymal transition, Transforming growth factor beta
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