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Epigenetic regulation of RTK signaling

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Abstract

Receptor tyrosine kinase (RTK) signaling cascades coordinate intracellular signaling in response to growth factors, chemokines, and other extracellular stimuli to control fundamental biological processes such as cellular proliferation, metabolism, and survival. Hyperactivation of pathways associated with growth factor signaling (e.g., RTK and downstream effectors including Ras, PI3K/AKT, and Raf) is a frequent event in human cancers, which uncouples ligand-mediated activation with signal transduction. While the contributions of direct genomic events are well understood as causative agents of hyperactive signal transduction, other non-heritable genomic modifications promote the activation of growth factor-associated signaling cascades. In this review, we highlight epigenomic mechanisms by which hyperactivation of RTK-associated signaling cascades occurs and may contribute to cancer.

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Acknowledgements

The authors apologize to the many colleagues whose work they were unable to cite due to space limitations. This work was supported by the American Cancer Society (125303-PF-13-097-01-CCE, to J.M.S) and the National Institutes of Health (P50 CA168504; P50 CA16596; CA187918-02, to T.M.R.).

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Authors and Affiliations

  1. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA

    Jennifer M Spangle & Thomas M Roberts

  2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

    Jennifer M Spangle & Thomas M Roberts

  3. Dana-Farber Cancer Institute, Boston, MA, 02115, USA

    Thomas M Roberts

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  1. Jennifer M Spangle
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  2. Thomas M Roberts
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Correspondence to Thomas M Roberts.

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Spangle, J.M., Roberts, T.M. Epigenetic regulation of RTK signaling. J Mol Med 95, 791–798 (2017). https://doi.org/10.1007/s00109-017-1546-0

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