title: Translational regulation of inhibin βA by TGFβ via the RNA-binding protein hnRNP E1 enhances the invasiveness of epithelial-to-mesenchymal transitioned cells.
abstract: 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)-β signaling pathway is a key inducer of EMT and we have elucidated a posttranscriptional mechanism by which TGFβ modulates expression of select transcripts via the RNA-binding protein hnRNP E1 during EMT. One such transcript inhibin βA is a member of the TGFβ superfamily. Here, we show by polysome profiling that inhibin βA is translationally regulated by TGFβ via hnRNP E1. TGFβ treatment or knockdown of hnRNP E1 relieves silencing of the inhibin βA transcript, resulting in increased protein expression and secreted levels of the inhibin βA homodimer, activin A. Our data indicate that the translational upregulation of inhibin βA enhances the migration and invasion of cells that have undergone an EMT and promotes cancer progression in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.|Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: B V
authors.initials: BV
authors.lastname: Howley
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.|Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Hussey
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.|Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.|Department of Biomedical Sciences, Kent State University, Kent, OH, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Link
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.|Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Howe
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000941:ethics; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000502:physiology*; D028322:Inhibin-beta Subunits / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D034622:RNA Interference / Q000187:drug effects; D016601:RNA-Binding Proteins; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C094604:PCBP1 protein, human; D016601:RNA-Binding Proteins; D016212:Transforming Growth Factor beta; C103008:inhibin beta A subunit; D028322:Inhibin-beta Subunits