Smyd3 Is a Transcriptional Potentiator of Multiple Cancer-Promoting Genes and Required for Liver and Colon Cancer Development

Cancer Cell. 2016 Mar 14;29(3):354-366. doi: 10.1016/j.ccell.2016.01.013. Epub 2016 Feb 18.


Smyd3 is a protein methyltransferase implicated in cancer development. Here we show that Smyd3 expression in mice is required for chemically induced liver and colon cancer formation. In these organs Smyd3 functions in the nucleus, stimulating the transcription of several key regulators involved in cell proliferation, epithelial-mesenchymal transition, the JAK/Stat3 oncogenic pathway, as well as the Myc and Ctnnb1 oncogenes. Smyd3 interacts with H3K4Me3-modified histone tails, which facilitates its recruitment to the core promoter regions of most active genes. Smyd3 binding density on target genes positively correlates with increased RNA polymerase-II density and transcriptional outputs. Despite its widespread distribution, the transcription-potentiating function of Smyd3 is restricted to a particular set of genes, whose expression is induced specifically during carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Cell Proliferation / genetics
  • Colonic Neoplasms / genetics*
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Histone-Lysine N-Methyltransferase / genetics*
  • Janus Kinases / genetics
  • Liver Neoplasms / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA Polymerase II / genetics
  • STAT3 Transcription Factor / genetics
  • Transcription, Genetic / genetics*
  • Transcriptional Activation / genetics
  • beta Catenin / genetics


  • CTNNB1 protein, mouse
  • Proto-Oncogene Proteins c-myc
  • STAT3 Transcription Factor
  • beta Catenin
  • Histone-Lysine N-Methyltransferase
  • Smyd3 protein, mouse
  • Janus Kinases
  • RNA Polymerase II