Identification of novel metastasis suppressor signaling pathways for breast cancer

Cell Cycle. 2012 Jul 1;11(13):2452-7. doi: 10.4161/cc.20624. Epub 2012 Jul 1.


Cancer lethality is mainly caused by metastasis. Therefore, understanding the nature of the genes involved in this process has become a priority. Given the heterogeneity of mutations in cancer cells, considerable focus has been directed toward characterizing metastasis genes in the context of relevant signaling pathways rather than treating genes as independent and equal entities. One signaling cascade implicated in the regulation of cell growth, invasion and metastasis is the MAP kinase pathway. Raf kinase inhibitory protein (RKIP) functions as an inhibitor of the MAP kinase pathway and is a metastasis suppressor in different cancer models. By utilizing statistical analysis of clinical data integrated with experimental validation, we recently identified components of the RKIP signaling pathway relevant to breast cancer metastasis. Using the RKIP pathway as an example, we show how prior biological knowledge can be efficiently combined with genome-wide patient data to identify gene regulatory mechanisms that control metastasis.

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.
  • Review

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phosphatidylethanolamine Binding Protein / metabolism
  • Signal Transduction*
  • Tumor Suppressor Proteins / metabolism*


  • Phosphatidylethanolamine Binding Protein
  • Tumor Suppressor Proteins
  • Mitogen-Activated Protein Kinase Kinases