Trefoil Factors: Gastrointestinal-specific Proteins Associated with Gastric Cancer

Trefoil factor family (TFF), composed of TFF1, TFF2, and TFF3, is a cluster of secreted peptides characterized by trefoil domain (s) and C-terminal dimerization domain. TFF1, a gastric tumor suppressor, is a single trefoil peptide originally detected in breast cancer cell lines but expressed mainly in the stomach; TFF2, a candidate of gastric cancer suppressor with two trefoil domains, is abundant in the stomach and duodenal Brunner's glands; and TFF3 is another single trefoil peptide expressed throughout the intestine which can promote the development of gastric carcinoma. According to multiple studies, TFFs play a regulatory function in the mammals' digestive system, namely in mucosal protection and epithelial cell reconstruction, tumor suppression or promotion, signal transduction and the regulation of proliferation and apoptosis. Action mechanisms of TFFs remain unresolved, but the recent demonstration of a GKN (gastrokine) 2-TFF1 heterodimer implicates structural and functional interplay with gastrokines. This review aims to encapsulate the structural and biological characteristics of TFF.