ArticleInternational journal of molecular sciences2018
TFF1 Promotes EMT-Like Changes through an Auto-Induction Mechanism.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 28 citations in OpenAlex.
- Machine Learning Analysis of RNA-Seq Data Identifies Key Gene Signatures and Pathways in Mpox Virus-Induced Gastrointestinal Complications Using Colon Organoid Models.International journal of molecular sciences · 2024Article
- Secretory Trefoil Factor 1 (TFF1) promotes gemcitabine resistance through chemokine receptor CXCR4 in Pancreatic Ductal Adenocarcinoma.Cancer letters · 2024Article
- Epithelial-Mesenchymal Transition (EMT).International journal of molecular sciences · 2023Article
- Towards a molecular understanding of the overlapping and distinct roles of UBQLN1 and UBQLN2 in lung cancer progression and metastasis.Neoplasia (New York, N.Y.) · 2022Article
- C/EBPα Epigenetically ModulatesFrontiers in immunology · 2022Article
- Trefoil factor family proteins as potential diagnostic markers for mucinous invasive ovarian carcinoma.Frontiers in oncology · 2022Article
- Trefoil Factor 1 Suppresses Epithelial-mesenchymal Transition through Inhibition of TGF-beta Signaling in Gastric Cancer Cells.Journal of cancer prevention · 2021Article
- TFF1 Induces Aggregation and Reduces Motility ofInternational journal of molecular sciences · 2021Article
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trefoil factor 1 (TFF1) is a small secreted protein expressed in the gastrointestinal tract where, together with the other two members of its family, it plays an essential role in mucosal protection and repair against injury. The molecular mechanisms involved in the protective function of all three TFF proteins are not fully elucidated. In this paper, we investigated the role of TFF1 in epithelial to mesenchymal transition (EMT) events. The effects of TFF1 on cellular models in normoxia and/or hypoxia were evaluated by western blot, immunofluorescence, qRT-PCR and trans-well invasion assays. Luciferase reporter assays were used to assess the existence of an auto-regulatory mechanism of TFF1. The methylation status of TFF1 promoter was measured by high-resolution melting (HRM) analysis. We demonstrate a TFF1 auto-induction mechanism with the identification of a specific responsive element located between -583 and -212 bp of its promoter. Our results suggest that TFF1 can regulate its own expression in normoxic, as well as in hypoxic, conditions acting synergistically with the hypoxia-inducible factor 1 (HIF-1α) pathway. Functionally, this auto-induction mechanism seems to promote cell invasion and EMT-like modifications in vitro. Additionally, exogenously added human recombinant TFF1 protein was sufficient to observe similar effects. Together, these findings suggest that the hypoxic conditions, which can be induced by gastric injury, promote TFF1 up-regulation, strengthened by an auto-induction mechanism, and that the trefoil peptide takes part in the epithelial-mesenchymal transition events eventually triggered to repair the damage.
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