{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:34:41Z","timestamp":1789695281276,"version":"4.0.1"},"reference-count":87,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,4,4]],"date-time":"2020-04-04T00:00:00Z","timestamp":1585958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>TFF1 is a protective peptide of the Trefoil Factor Family (TFF), which is co-secreted with the mucin MUC5AC, gastrokine 2 (GKN2), and IgG Fc binding protein (FCGBP) from gastric surface mucous cells. Tff1-deficient mice obligatorily develop antropyloric adenoma and about 30% progress to carcinomas, indicating that Tff1 is a tumor suppressor. As a hallmark, TFF1 contains seven cysteine residues with three disulfide bonds stabilizing the conserved TFF domain. Here, we systematically investigated the molecular forms of TFF1 in the human gastric mucosa. TFF1 mainly occurs in an unusual monomeric form, but also as a homodimer. Furthermore, minor amounts of TFF1 form heterodimers with GKN2, FCGBP, and an unknown partner protein, respectively. TFF1 also binds to the mucin MUC6 in vitro, as shown by overlay assays with synthetic 125I-labeled TFF1 homodimer. The dominant presence of a monomeric form with a free thiol group at Cys-58 is in agreement with previous studies in Xenopus laevis and mouse. Cys-58 is likely highly reactive due to flanking acid residues (PPEEEC58EF) and might act as a scavenger for extracellular reactive oxygen\/nitrogen species protecting the gastric mucosa from damage by oxidative stress, e.g., H2O2 generated by dual oxidase (DUOX).<\/jats:p>","DOI":"10.3390\/ijms21072508","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T06:10:28Z","timestamp":1586153428000},"page":"2508","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["The Tumor Suppressor TFF1 Occurs in Different Forms and Interacts with Multiple Partners in the Human Gastric Mucus Barrier: Indications for Diverse Protective Functions"],"prefix":"10.3390","volume":"21","author":[{"given":"J\u00f6rn","family":"Heuer","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Heuer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"St\u00fcrmer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f6nke","family":"Harder","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-7036","authenticated-orcid":false,"given":"Hartmut","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7835-9636","authenticated-orcid":false,"given":"Nayara","family":"Braga Emidio","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1996-4646","authenticated-orcid":false,"given":"Markus","family":"Muttenthaler","sequence":"additional","affiliation":[{"name":"Institute for Molecular Biosciences, The University of Queensland, Brisbane, Queensland 4072, Australia"},{"name":"Institute of Biological Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f6rthe","family":"Jechorek","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0031-9540","authenticated-orcid":false,"given":"Werner","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Medicinal Chemistry, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,4]]},"reference":[{"key":"ref_1","first-page":"F61","article-title":"The pS2\/TFF1 trefoil factor, from basic research to clinical applications","volume":"1378","author":"Ribieras","year":"1998","journal-title":"Biochim. 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