Notch and Mef2 synergize to promote proliferation and metastasis through JNK signal activation in Drosophila

EMBO J. 2012 Jun 29;31(13):2895-907. doi: 10.1038/emboj.2012.129. Epub 2012 May 11.

Abstract

Genetic analyses in Drosophila revealed a synergy between Notch and the pleiotropic transcription factor Mef2 (myocyte enhancer factor 2), which profoundly influences proliferation and metastasis. We show that these hyperproliferative and invasive Drosophila phenotypes are attributed to upregulation of eiger, a member of the tumour necrosis factor superfamily of ligands, and the consequent activation of Jun N-terminal kinase signalling, which in turn triggers the expression of the invasive marker MMP1. Expression studies in human breast tumour samples demonstrate correlation between Notch and Mef2 paralogues and support the notion that Notch-MEF2 synergy may be significant for modulating human mammary oncogenesis.

Publication types

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

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Proliferation*
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / metabolism*
  • Female
  • Gene Expression Profiling
  • Humans
  • MAP Kinase Signaling System / physiology*
  • MEF2 Transcription Factors
  • Male
  • Matrix Metalloproteinase 1 / metabolism
  • Membrane Proteins / biosynthesis
  • Myogenic Regulatory Factors / metabolism
  • Myogenic Regulatory Factors / physiology*
  • Neoplasm Metastasis
  • Receptors, Notch / physiology*
  • Up-Regulation

Substances

  • Drosophila Proteins
  • MEF2 Transcription Factors
  • Mef2 protein, Drosophila
  • Membrane Proteins
  • Myogenic Regulatory Factors
  • N protein, Drosophila
  • Receptors, Notch
  • egr protein, Drosophila
  • Matrix Metalloproteinase 1