dMyc Transforms Cells Into Super-Competitors

Cell. 2004 Apr 2;117(1):117-29. doi: 10.1016/s0092-8674(04)00262-4.

Abstract

Overexpression of myc protooncogenes has been implicated in the genesis of many human tumors. Myc proteins seem to regulate diverse biological processes, but their role in tumorigenesis remains enigmatic. Here we use Drosophila imaginal discs to mimic situations in which cells with unequal levels of Myc protein are apposed and show that this invariably elicits a win/lose situation reminiscent of cell competition; cells with lower levels of dMyc are eliminated by apoptosis whereas cells with higher levels of dMyc over-proliferate. We find that this competitive behavior correlates with, and can be corrected by, the activation of the BMP/Dpp survival signaling pathway. Hence the heritable increase in dMyc levels causes cells to behave as "super-competitors" and reveals a novel mode of clonal expansion that causes, but also relies on, the killing of surrounding cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Bone Morphogenetic Proteins / metabolism
  • Cell Communication / genetics
  • Cell Differentiation / genetics*
  • Cell Division / genetics
  • Cell Survival / genetics*
  • Clone Cells / metabolism
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism*
  • Gene Expression Regulation, Developmental / genetics
  • Morphogenesis / genetics
  • Organogenesis / genetics*
  • Signal Transduction / genetics
  • Transcription Factors / metabolism*
  • Wings, Animal / cytology
  • Wings, Animal / growth & development
  • Wings, Animal / metabolism

Substances

  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Myc protein, Drosophila
  • Transcription Factors
  • dpp protein, Drosophila