Hoffmann Werner
Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke-University Magdeburg, D-39120 Magdeburg, Germany.
Int J Oncol. 2015 Sep;47(3):806-16. doi: 10.3892/ijo.2015.3090. Epub 2015 Jul 17.
The peptide TFF2 (formerly 'spasmolytic polypeptide'), a member of the trefoil factor family (TFF) containing two TFF domains, is mainly expressed together with the mucin MUC6 in the gastric epithelium and duodenal Brunner's glands. Pathologically, TFF2 expression is observed ectopically during stone diseases, chronic inflammatory conditions and in several metaplastic and neoplastic epithelia; most prominent being the 'spasmolytic polypeptide-expressing metaplasia' (SPEM), which is an established gastric precancerous lesion. TFF2 plays a critical role in maintaining gastric mucosal integrity and appears to restrain tumorigenesis in the stomach. Recently, porcine TFF2 has been shown to interact with the gastric mucin MUC6 and thus stabilize the gastric mucus barrier. On the one hand, TFF2 binds to MUC6 via non-covalent lectin interactions with the glycotope GlcNAcα1→4Galβ1→R. On the other hand, TFF2 is probably also covalently bound to MUC6 via disulfide bridges. Thus, implications for the complex multimeric assembly, cross-linking, and packaging of MUC6 as well as the rheology of gastric mucus are discussed in detail in this review. Furthermore, TFF2 is also expressed in minor amounts in the immune and nervous systems. Thus, similar to galectins, its lectin activity would perfectly enable TFF2 to form multivalent complexes and cross-linked lattices with a plethora of transmembrane glycoproteins and thus modulate different signal transduction processes. This could explain the multiple and diverse biological effects of TFF2 [e.g., motogenic, (anti)apoptotic, and angiogenic effects]. Finally, a function during fertilization is also possible for TFF domains because they occur as shuffled modules in certain zona pellucida proteins.
肽TFF2（以前称为“解痉多肽”）是三叶因子家族（TFF）的成员，含有两个TFF结构域，主要与粘蛋白MUC6一起在胃上皮和十二指肠布伦纳腺中表达。在病理情况下，在结石疾病、慢性炎症状态以及几种化生和肿瘤上皮中可观察到TFF2的异位表达；最显著的是“表达解痉多肽的化生”（SPEM），这是一种已确定的胃癌前病变。TFF2在维持胃黏膜完整性方面起关键作用，并且似乎抑制胃中的肿瘤发生。最近，已证明猪TFF2与胃粘蛋白MUC6相互作用，从而稳定胃黏液屏障。一方面，TFF2通过与糖基表位GlcNAcα1→4Galβ1→R的非共价凝集素相互作用与MUC6结合。另一方面，TFF2可能也通过二硫键与MUC6共价结合。因此，本综述详细讨论了MUC6的复杂多聚体组装、交联和包装以及胃黏液的流变学。此外，TFF2在免疫和神经系统中也有少量表达。因此，与半乳糖凝集素类似，其凝集素活性将完美地使TFF2与大量跨膜糖蛋白形成多价复合物和交联晶格，从而调节不同的信号转导过程。这可以解释TFF2的多种不同生物学效应[例如，促运动、（抗）凋亡和血管生成效应]。最后，TFF结构域在受精过程中也可能发挥作用，因为它们在某些透明带蛋白中作为重排模块出现。
