{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTFF1 is a small, secreted peptide originally characterized in the gastric mucosa that plays a critical role in mucosal protection, restitution, and tumor suppression. In normal stomach epithelia, TFF1 contributes to maintaining barrier function and integrity by promoting epithelial repair and by modulating cell‐cycle regulators such as cyclin‐dependent kinase inhibitors, thereby delaying the G1–S transition. Its gene expression is dynamically regulated by epigenetic mechanisms – including cyclic, strand‐specific methylation/demethylation on its promoter – and its inactivation through promoter methylation or loss of heterozygosity has been implicated in the initiation and progression of gastric carcinogenesis. Moreover, TFF1 predominantly forms disulfide‐linked heterodimers (for example with the binding partner TFIZ1), and, by inhibiting inflammatory signaling cascades such as the TNF‑α–mediated NF‑κB pathway and the IL6–STAT3 axis, TFF1 further exerts tumor‐suppressive effects in the stomach."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its protective role in the gastric mucosa, TFF1 modulates epithelial restitution and cell motility in a context‐dependent manner. Studies in breast cancer cells, for instance, have revealed that TFF1 can influence cell proliferation, migration, and invasive behavior—sometimes exerting anti‐proliferative and pro‑apoptotic effects (via p53 activation and modulation of specific microRNAs) while in other experimental systems its expression is associated with increased migration or anchorage‐independent growth. Such apparently paradoxical actions underscore that TFF1’s impact on oncogenesis may vary with the tissue type and microenvironment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in mucosal protection and tumor suppression, TFF1 functions as a divalent lectin that interacts with mucin‐type O‑glycans, thereby modulating the viscoelastic properties of the mucus layer. It can bind specific receptors and partners—notably the mechanosensitive protein Piezo1 and TFIZ1—to mediate bacterial interactions (as seen in its avid binding to Helicobacter pylori) and to influence biomolecular signaling cascades. Owing to its stable secretion and detectable presence in biological fluids, TFF1 is also being explored as a non‐invasive biomarker in diverse pathologies, including colorectal lesions, necrotizing enterocolitis, and urinary tract disorders, with assays such as ELISA aiding in its quantification for diagnostic and prognostic purposes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Carine Bossenmeyer-Pourié, Rama Kannan, Stéphane Ribieras, et al. 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