Translational regulation of inhibin βA by TGFβ via the RNA-binding protein hnRNP E1 enhances the invasiveness of epithelial-to-mesenchymal transitioned cells

The epithelial-to-mesenchymal transition (EMT) is a cellular process that functions during embryonic development and tissue regeneration, thought to be aberrantly activated in epithelial-derived cancer and has an important role in the process of metastasis. The transforming growth factor (TGF)-beta signaling pathway is a key inducer of EMT and we have elucidated a posttranscriptional mechanism by which TGF beta modulates expression of select transcripts via the RNA-binding protein hnRNP E1 during EMT. One such transcript inhibin beta A is a member of the TGF beta superfamily. Here, we show by polysome profiling that inhibin beta A is translationally regulated by TGF beta via hnRNP E1. TGF beta treatment or knockdown of hnRNP E1 relieves silencing of the inhibin beta A transcript, resulting in increased protein expression and secreted levels of the inhibin beta A homodimer, activin A. Our data indicate that the translational upregulation of inhibin beta A enhances the migration and invasion of cells that have undergone an EMT and promotes cancer progression in vivo.