Supercompetitor status of Drosophila Myc cells requires p53 as a fitness sensor to reprogram metabolism and promote viability

Cell Metab. 2014 Mar 4;19(3):470-83. doi: 10.1016/j.cmet.2014.01.012. Epub 2014 Feb 20.


In growing tissues, cell fitness disparities can provoke interactions that promote stronger cells at the expense of the weaker in a process called cell competition. The mechanistic definition of cell fitness is not understood, nor is it understood how fitness differences are recognized. Drosophila cells with extra Myc activity acquire "supercompetitor" status upon confrontation with wild-type (WT) cells, prompting the latter's elimination via apoptosis. Here we show that such confrontation enhances glycolytic flux in Myc cells and promotes their fitness and proliferation in a p53-dependent manner. Whereas p53 loss in noncompeting Myc cells is inconsequential, its loss impairs metabolism, reduces viability, and prevents the killing activity of Myc supercompetitor cells. We propose that p53 acts as a general sensor of competitive confrontation to enhance the fitness of the "winner" population. Our findings suggest that the initial confrontation between precancerous and WT cells could enhance cancer cell fitness and promote tumor progression.

Publication types

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

MeSH terms

  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Drosophila / cytology
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Genomic Instability
  • Glycolysis
  • Oxidative Phosphorylation
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*


  • Drosophila Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Tumor Suppressor Protein p53