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Trefoil factor 3 peptide regulates migration via a Twist-dependent pathway in gastric cell
Authors:Qianqian Zheng  Jian Gao  Honglin Li  Wendong Guo  Qi Mao  Enhui Gao  Ya-qin Zhu
Institution:1. Division of Cell Pathobiology, Key Laboratory of Medical Cell Biology, Ministry of Education, Department of Cell Biology, College of Basic Medical Science, China Medical University, China;2. Cardiovascular Institute of China Medical University, China;3. Center of Laboratory Technology and Experimental Medicine, China Medical University, China;4. Department of Biochemistry and Molecular Biology, Georgia Health Sciences University, United States
Abstract: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.
Keywords:TFF3  trefoil factor 3  ITF  intestinal trefoil factor  ZO-1  zonula occludens protein 1  CK-8  cytokeratin 8  siRNA  small interfering RNA  HRP  Horseradish peroxidase
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