Emerging role of PI3K/AKT in tumor-related epigenetic regulation

Semin Cancer Biol. 2019 Dec:59:112-124. doi: 10.1016/j.semcancer.2019.04.001. Epub 2019 Apr 2.

Abstract

Epigenetic alterations, along with genetic alterations, have long been regarded as the most important mechanism participating in carcinogenesis. DNA methylation, histone modifications, and RNA-mediated regulation are involved in many cellular processes that are essential to cancer initiation and progression. A plethora of chromatin-associated proteins and modifying proteins take control of these processes and they are under the modulation of signaling pathways. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway (PI3K/AKT) is in manage of multiple biological processes and is frequently aberrantly activated in human cancers. Increasing evidence has demonstrated that critical epigenetic modifiers are directly or indirectly modulated by PI3K/AKT signaling, and participate in oncogenicity of PI3K cascade in cancers. In this review, we revisit the mechanism of the PI3K/AKT signaling pathway modulating epigenetic reprogramming in cancer and attempt to establish the connection between PI3K/AKT cascade and the epigenome.

Keywords: DNA methylation; Epigenetic modifications; Histone methylation/acetylation; Non-coding RNAs; PI3K/AKT pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Methylation
  • Disease Susceptibility*
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Neoplastic*
  • Histones / metabolism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA, Untranslated / metabolism
  • Signal Transduction

Substances

  • Histones
  • RNA, Untranslated
  • Proto-Oncogene Proteins c-akt