Raf kinase inhibitory protein (RKIP) as a metastasis suppressor: regulation of signaling networks in cancer

Crit Rev Oncog. 2014;19(6):447-54. doi: 10.1615/critrevoncog.2014012000.


Cancer is one of the deadliest diseases worldwide, accounting for about 8 million deaths a year. For solid tumors, cancer patients die as a result of the metastatic spread of the tumor to the rest of the body. Therefore, there is a clinical need for understanding the molecular and cellular basis of metastasis, identifying patients whose tumors are more likely to metastasize, and developing effective therapies against metastatic progression. Over the years, Raf kinase inhibitory protein (RKIP) has emerged as a natural suppressor of the metastatic process, constituting a tool for studying metastasis and its clinical outcomes. Here, we review RKIP's role as a metastasis suppressor and the signaling networks and genes regulated by RKIP in metastatic, triple-negative breast cancer. We also highlight the clinical implications and power of building gene signatures based on RKIP-regulated signaling modules in identifying cancer patients that are at higher risk for metastases. Finally, we highlight the potential of RKIP as a tool for developing new therapeutic strategies in cancer treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • Genes, Tumor Suppressor*
  • Humans
  • MAP Kinase Signaling System / physiology
  • Neoplasm Metastasis / genetics*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Phosphatidylethanolamine Binding Protein / physiology*
  • Signal Transduction / genetics
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology


  • PEBP1 protein, human
  • Phosphatidylethanolamine Binding Protein