Epigenetic regulation of RTK signaling

J Mol Med (Berl). 2017 Aug;95(8):791-798. doi: 10.1007/s00109-017-1546-0. Epub 2017 Jun 6.

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.

Keywords: Cancer; Epigenetics; Receptor tyrosine kinases; Signal transduction.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / therapeutic use
  • DNA Methylation
  • Drug Resistance, Neoplasm / genetics
  • Epigenesis, Genetic
  • Genes, Tumor Suppressor
  • Histone Deacetylases / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents, Hormonal
  • Intercellular Signaling Peptides and Proteins
  • Receptor Protein-Tyrosine Kinases
  • Histone Deacetylases