Trefoil factor 3 peptide regulates migration via a Twist-dependent pathway in gastric cell

•Up-regulated expression of Twist is revealed in TFF3-overexpression SGC7901 cells.•Twist is required for TFF3-enhanced migration in SGC7901 cells.•CK-8, ZO-1 and MMP-9 modulated by TFF3 is Twist-dependent in cell migration.•Silenced expression of Twist inhibited the migration induced by TFF3. Trefoil factor 3 (TFF3) is a member of the TFF-domain peptide family and essential in regulating cell migration and maintaining mucosal integrity in gastrointestinal tract. However, the role of TFF3 and its downstream regulating mechanisms in cancer cell migration remain unclear. We previously reported that TFF3 prolonged the up-regulation of Twist protein to modulate IL-8 secretion in intestinal epithelial cells. In this study, we investigated the role of Twist protein in TFF3-induced migration of SGC7901 cells. While Twist was activated by TFF3, siRNA-mediated knockdown of Twist abolished TFF3-induced cell migration. Furthermore, the migration related marker CK-8 as well as ZO-1 and MMP-9 was also regulated by TFF3 via a Twist-dependent mechanism. Our study suggests that Twist, as an important potential downstream effector, plays a key role in TFF3-modulated metastasis in gastric cancer and can be a promising therapeutic target against intestinal-type gastric cancer.