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Chemical synthesis of human trefoil factor 1 (TFF1) and its homodimer provides novel insights into their mechanisms of action.

ABSTRACT: TFF1 is a key peptide for gastrointestinal protection and repair. Its molecular mechanism of action remains poorly understood with synthetic intractability a recognised bottleneck. Here we describe the synthesis of TFF1 and its homodimer and their interactions with mucins and Helicobacter pylori. Synthetic access to TFF1 is an important milestone for probe and therapeutic development.

SUBMITTER: Braga Emidio N

PROVIDER: S-EPMC7116170 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Chemical synthesis of human trefoil factor 1 (TFF1) and its homodimer provides novel insights into their mechanisms of action.

Braga Emidio Nayara N Baik Hayeon H Lee David D Stürmer René R Heuer Jörn J Elliott Alysha G AG Blaskovich Mark A T MAT Haupenthal Katharina K Tegtmeyer Nicole N Hoffmann Werner W Schroeder Christina I CI Muttenthaler Markus M

Chemical communications (Cambridge, England) 20200511 47

TFF1 is a key peptide for gastrointestinal protection and repair. Its molecular mechanism of action remains poorly understood with synthetic intractability a recognised bottleneck. Here we describe the synthesis of TFF1 and its homodimer and their interactions with mucins and Helicobacter pylori. Synthetic access to TFF1 is an important milestone for probe and therapeutic development. ...[more]

PMID: 32391824

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Deficiency in trefoil factor 1 (TFF1) increases tumorigenicity of human breast cancer cells and mammary tumor development in TFF1-knockout mice.

Project description:Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover, controversial data have been reported. TFF1 function in the mammary gland therefore needs to be clarified. In this study, using retroviral vectors, we performed TFF1 gain- or loss-of-function experiments in four human mammary epithelial cell lines: normal immortalized TFF1-negative MCF10A, malignant TFF1-negative MDA-MB-231 and malignant TFF1-positive MCF7 and ZR75.1. The expression of TFF1 stimulated the migration and invasion in the four cell lines. Forced TFF1 expression in MCF10A, MDA-MB-231 and MCF7 cells did not modify anchorage-dependent or -independent cell proliferation. By contrast, TFF1 knockdown in MCF7 enhanced soft-agar colony formation. This increased oncogenic potential of MCF7 cells in the absence of TFF1 was confirmed in vivo in nude mice. Moreover, chemically induced tumorigenesis in TFF1-deficient (TFF1-KO) mice led to higher tumor incidence in the mammary gland and larger tumor size compared with wild-type mice. Similarly, tumor development was increased in the TFF1-KO ovary and lung. Collectively, our results clearly show that TFF1 does not exhibit oncogenic properties, but rather reduces tumor development. This beneficial function of TFF1 is in agreement with many clinical studies reporting a better outcome for patients with TFF1-positive breast primary tumors.

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Expression of Trefoil Factor 1 (TFF1) in Cancer: A Tissue Microarray Study Involving 18,878 Tumors.

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