RESUMEN
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)-ß signaling pathway is a key inducer of EMT and we have elucidated a posttranscriptional mechanism by which TGFß modulates expression of select transcripts via the RNA-binding protein hnRNP E1 during EMT. One such transcript inhibin ßA is a member of the TGFß superfamily. Here, we show by polysome profiling that inhibin ßA is translationally regulated by TGFß via hnRNP E1. TGFß treatment or knockdown of hnRNP E1 relieves silencing of the inhibin ßA transcript, resulting in increased protein expression and secreted levels of the inhibin ßA homodimer, activin A. Our data indicate that the translational upregulation of inhibin ßA enhances the migration and invasion of cells that have undergone an EMT and promotes cancer progression in vivo.
