J Cancer Prev.  2021 Jun;26(2):137-144. 10.15430/JCP.2021.26.2.137.

Trefoil Factor 1 Suppresses Epithelial-mesenchymal Transition through Inhibition of TGF-beta Signaling in Gastric Cancer Cells

• Lee DY
• Song MY
• Kim EH

• KMID: 2517365
• DOI: http://doi.org/10.15430/JCP.2021.26.2.137

Abstract

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. Upregulation 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.

Keyword

Gastric cancer; Trefoil factor 1; Epithelial-mesenchymal transition; Transforming growth factor beta