Histone demethylase RBP2 is critical for breast cancer progression and metastasis

Cell Rep. 2014 Mar 13;6(5):868-77. doi: 10.1016/j.celrep.2014.02.004. Epub 2014 Feb 27.


Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers and roles of such epigenetic changes in tumor metastasis are still poorly understood. Using bioinformatic analysis of human breast cancer gene-expression data sets, we identified histone demethylase RBP2 as a putative mediator of metastatic progression. By using both human breast cancer cells and genetically engineered mice, we demonstrated that RBP2 is critical for breast cancer metastasis to the lung in multiple in vivo models. Mechanistically, RBP2 promotes metastasis as a pleiotropic positive regulator of many metastasis genes, including TNC. In addition, RBP2 loss suppresses tumor formation in MMTV-neu transgenic mice. These results suggest that therapeutic targeting of RBP2 is a potential strategy for inhibition of tumor progression and metastasis.

MeSH terms

  • Animals
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Humans
  • Male
  • Mammary Neoplasms, Experimental / enzymology
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Neoplasm Metastasis
  • Retinol-Binding Proteins, Cellular / genetics
  • Retinol-Binding Proteins, Cellular / metabolism*
  • Transfection


  • RBP2 protein, human
  • Retinol-Binding Proteins, Cellular
  • Histone Demethylases

Associated data

  • GEO/GSE49119