Novel c-MYC target genes mediate differential effects on cell proliferation and migration

EMBO Rep. 2007 Jan;8(1):70-6. doi: 10.1038/sj.embor.7400849. Epub 2006 Dec 8.


The developmental and oncogenic roles of MYC proteins are well established, but the transcriptional targets mediating their functions remain elusive. Using small interfering RNA-mediated knockdown in breast and cervix carcinoma cell lines, which overexpress c-MYC, we show that c-MYC independently controls metabolism and cell proliferation, and can, depending on the cells, promote or inhibit migration. We identified new c-MYC target genes in these cell lines, and show that selective regulation of some targets correlates with the phenotypic responses of these different cell lines to c-MYC depletion. Notably, we show that a positive regulation of the WNT signalling pathway contributes to c-MYC pro-mitogenic effects in breast and cervix carcinoma cells. We also show that repression of CCL5/RANTES accounts for c-MYC anti-migratory effects in specific breast cancer cells. Our combined genomic and phenotypic analysis indicates that c-MYC functions are cellular-context-dependent and that selectively regulated genes are responsible for its differential properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics*
  • Cell Proliferation / drug effects
  • Chemokine CCL5 / genetics
  • Chemokines, CC / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Proto-Oncogene Proteins c-myc / physiology*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Repressor Proteins / physiology*
  • Signal Transduction / genetics
  • Wnt Proteins / genetics


  • CCL5 protein, human
  • Chemokine CCL5
  • Chemokines, CC
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • Repressor Proteins
  • Wnt Proteins