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

Oncogene volume 35, pages 1725–1735 (2016)Cite this article

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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.

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Acknowledgements

This work was supported by Grants CA055536 and CA154663 from the National Cancer Institute. BVH was supported by funding from the Abney Foundation. GSH was supported by an American Heart Association Pre-doctoral Fellowship 10PRE3870024. This study used the services of the MUSC Center for Oral Health Research (COHR), which is partially supported by the National Institute of General Medicine grant P30GM103331, the MUSC Flow Cytometry Facility which is supported by P30GM103342, the Cell & Molecular Imaging Shared Resource of MUSC supported by P30CA138313, the Biorepository & Tissue Analysis Shared Resource, Hollings Cancer Center, MUSC and the Gene Targeting and Knockout Shared Resource at MUSC. We would like to thank Maya El Sabban for assisting us with xenograft experiments.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA

    B V Howley, G S Hussey, L A Link & P H Howe

  2. Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA

    B V Howley, G S Hussey, L A Link & P H Howe

  3. Department of Biomedical Sciences, Kent State University, Kent, OH, USA

    L A Link

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  1. B V Howley
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Correspondence to P H Howe.

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Howley, B., Hussey, G., Link, L. et al. Translational regulation of inhibin βA by TGFβ via the RNA-binding protein hnRNP E1 enhances the invasiveness of epithelial-to-mesenchymal transitioned cells. Oncogene 35, 1725–1735 (2016). https://doi.org/10.1038/onc.2015.238

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