Invasion of v-Fos(FBR)-transformed cells is dependent upon histone deacetylase activity and suppression of histone deacetylase regulated genes

Oncogene. 2004 Jul 8;23(31):5284-92. doi: 10.1038/sj.onc.1207687.


Transformation of fibroblasts with the v-fos oncogene produces a highly invasive phenotype that is mediated by changes in gene expression. Inhibition of histone deacetylase (HDAC) activity with trichostatin A (TSA) or valproic acid (VPA) at concentrations that do not affect morphology, motility, chemotaxis or proliferation, strongly inhibits invasion and results in the re-expression of a significant proportion of those genes that are downregulated in the v-Fos-transformed cells. Independent expression of three of these re-expressed genes, (Ring1 and YY1 binding protein (RYBP); protocadherin gamma subfamily C,3 (PCDHGC3); and signal transducer and activator of transcription 6 (STAT6)) in Fos-transformed cells, has no effect on morphology, motility, chemotaxis or proliferation, but strongly inhibits invasion. Therefore, we conclude that the ability of v-Fos-transformed cells to invade is dependent upon repression of gene expression through either direct or indirect HDAC activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cadherin Related Proteins
  • Cadherins / metabolism
  • Cell Division
  • Cell Line
  • Cell Line, Transformed
  • Cell Movement
  • Cell Transformation, Neoplastic
  • Chemotaxis
  • Cloning, Molecular
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Gene Expression Regulation, Enzymologic*
  • Histone Deacetylases / metabolism*
  • Hydroxamic Acids / pharmacology
  • Microscopy, Confocal
  • Microscopy, Phase-Contrast
  • Neoplasm Invasiveness
  • Oncogene Proteins v-fos / metabolism*
  • Phenotype
  • RNA / metabolism
  • Rats
  • Repressor Proteins / biosynthesis
  • STAT6 Transcription Factor
  • Trans-Activators / metabolism
  • Transfection
  • Valproic Acid / pharmacology


  • Actins
  • Cadherin Related Proteins
  • Cadherins
  • Gamma-protocadherins
  • Hydroxamic Acids
  • Oncogene Proteins v-fos
  • Repressor Proteins
  • Rybp protein, mouse
  • STAT6 Transcription Factor
  • Trans-Activators
  • trichostatin A
  • Valproic Acid
  • RNA
  • Histone Deacetylases