TFF1 (trefoil factor 1) is a secretory peptide that functions primarily as a stabilizer and protective component of the gastrointestinal mucous gel 1. It is co-expressed and co-secreted with gastric mucin MUC5AC in surface foveolar cells, maintaining the physical barrier against noxious agents 2. TFF1 exhibits pH-dependent lectin properties with carbohydrate-binding capacity, mediating interactions with pathogenic organisms like Helicobacter pylori through glycan recognition, potentially restricting bacterial localization within the mucus layer 2. In cancer biology, TFF1 shows complex, context-dependent roles. It functions as a tumor suppressor in gastric cancer, possibly regulating Lgr5+ antral stem cells and limiting dysregulated self-renewal 3. TFF1 polymorphisms significantly influence gastric carcinoma susceptibility, with the rs2156310 variant reducing predisposition in younger populations 4. However, TFF1 demonstrates tumor-promoting activity in breast and lung cancers, where its high expression correlates with worse immunotherapy response and increased TGFβ signaling activation 56. In breast cancer, elevated TFF1 paradoxically predicts favorable prognosis and hormonotherapy response 1. These divergent associations suggest tissue-specific and context-dependent functions in cancer pathogenesis and therapeutic response.