Jul 8, 2016

Foxc1 Controls Cell Fate Decisions During Transforming Growth Factor β Induced Epithelial to Mesenchymal Transition Through the Regulation of Fibroblast Growth Factor Receptor 1 Expression.

BioRxiv : the Preprint Server for Biology
Alexander HopkinsFred B Berry

Abstract

Epithelial to mesenchymal transition (EMT) is an important physiological process that drives tissue formation during development but also contributes to disease pathogenesis including fibrosis and cancer metastasis. The forkhead box transcription factor gene FOXC1 is an important developmental regulator in the generation of mesenchymal cells necessary in the formation of the anterior segment of the eye, the craniofacial skeleton and the meninges. Recently elevated expression of FOXC1 has been detected in several metastatic cancers that have undergone EMT events. We sought to determine the role of FOXC1 in the initiation of EMT events using NMuMG cells treated with TFGβ1. We found that although Foxc1 expression was increased following TFGβ1 induced EMT, Foxc1 was not required for this induction. Instead we propose that Foxc1 is required for the specification of the mesenchyme cell type, promoting an activated fibroblast phenotype over a myofibroblast phenotype following the initiation of EMT. This cells type specification was achieved through the regulation of Fibroblast growth factor (Fgfr) 1 expression. Using an RNA sequencing approach, we determined that levels of Fgfr1 normally activated upon TFGβ1 treatment were reduced in ...Continue Reading

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Mentioned in this Paper

Recombinant Transforming Growth Factor
Pathogenic Aspects
Inflammatory Myofibroblastic Tumor
Transforming Growth Factor beta
FGFR1
Cell Fate
Meninges
Fibroblast Growth Factor Receptor 1
Pathogenesis
Anterior Segment

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