HDAC6-Dependent Functions in Tumor Cells: Crossroad with the MAPK Pathways

Crit Rev Oncog. 2015;20(1-2):65-81. doi: 10.1615/critrevoncog.2014012484.

Abstract

Histone deacetylase 6 (HDAC6) is emerging as a novel therapeutic target in cancer treatment. HDAC6 plays an important role in cell migration, cell transformation, and DNA damage response. Our and others' studies have linked HDAC6's functions and HDAC6's regulation to the mitogen-activated protein kinase (MAPK) pathways. In particular, HDAC6's activity has been found to be regulated by EGF-EGFR-Ras-Raf-MEK-ERK signaling. Inversely, HDAC6 has been reported to modulate the functions of EGFR and Ras. In this review, we summarize the literature on HDAC6 and MAPK pathways, and emphasize the interaction between HDAC6 and the ERK-MAPK signaling cascade.

Publication types

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

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Transformation, Neoplastic / genetics
  • Histone Deacetylase 6
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histone Deacetylases / chemistry
  • Histone Deacetylases / physiology*
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Neoplasm Metastasis
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Protein Conformation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Histone Deacetylase Inhibitors
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinases
  • HDAC6 protein, human
  • Histone Deacetylase 6
  • Histone Deacetylases