MYC regulation of a "poor-prognosis" metastatic cancer cell state

Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3698-703. doi: 10.1073/pnas.0914203107. Epub 2010 Feb 4.

Abstract

Gene expression signatures are used in the clinic as prognostic tools to determine the risk of individual patients with localized breast tumors developing distant metastasis. We lack a clear understanding, however, of whether these correlative biomarkers link to a common biological network that regulates metastasis. We find that the c-MYC oncoprotein coordinately regulates the expression of 13 different "poor-outcome" cancer signatures. In addition, functional inactivation of MYC in human breast cancer cells specifically inhibits distant metastasis in vivo and invasive behavior in vitro of these cells. These results suggest that MYC oncogene activity (as marked by "poor-prognosis" signature expression) may be necessary for the translocation of poor-outcome human breast tumors to distant sites.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Movement / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasm Metastasis
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Proto-Oncogene Proteins c-myc / metabolism*

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-myc