TFF1 Promotes EMT-Like Changes through an Auto-Induction Mechanism

International Journal of Molecular Sciences
Elena RomanoAlessandra Tosco

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...Continue Reading

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Citations

Dec 19, 2019·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yuxuan HanKentaro Semba
Jun 26, 2020·Physiological Reviews·Paul J DavisHung-Yun Lin
Mar 7, 2021·International Journal of Molecular Sciences·Daniela ElettoAlessandra Tosco

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