DEAD-box helicase DP103 defines metastatic potential of human breast cancers

J Clin Invest. 2014 Sep;124(9):3807-24. doi: 10.1172/JCI73451. Epub 2014 Aug 1.


Despite advancement in breast cancer treatment, 30% of patients with early breast cancers experience relapse with distant metastasis. It is a challenge to identify patients at risk for relapse; therefore, the identification of markers and therapeutic targets for metastatic breast cancers is imperative. Here, we identified DP103 as a biomarker and metastasis-driving oncogene in human breast cancers and determined that DP103 elevates matrix metallopeptidase 9 (MMP9) levels, which are associated with metastasis and invasion through activation of NF-κB. In turn, NF-κB signaling positively activated DP103 expression. Furthermore, DP103 enhanced TGF-β-activated kinase-1 (TAK1) phosphorylation of NF-κB-activating IκB kinase 2 (IKK2), leading to increased NF-κB activity. Reduction of DP103 expression in invasive breast cancer cells reduced phosphorylation of IKK2, abrogated NF-κB-mediated MMP9 expression, and impeded metastasis in a murine xenograft model. In breast cancer patient tissues, elevated levels of DP103 correlated with enhanced MMP9, reduced overall survival, and reduced survival after relapse. Together, these data indicate that a positive DP103/NF-κB feedback loop promotes constitutive NF-κB activation in invasive breast cancers and activation of this pathway is linked to cancer progression and the acquisition of chemotherapy resistance. Furthermore, our results suggest that DP103 has potential as a therapeutic target for breast cancer treatment.

Publication types

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

MeSH terms

  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • DEAD Box Protein 20 / analysis
  • DEAD Box Protein 20 / genetics
  • DEAD Box Protein 20 / physiology*
  • Female
  • Humans
  • I-kappa B Kinase / metabolism
  • MAP Kinase Kinase Kinases / physiology
  • Matrix Metalloproteinase 9 / analysis
  • Matrix Metalloproteinase 9 / genetics
  • NF-kappa B / physiology
  • Neoplasm Invasiveness
  • Neoplasm Metastasis


  • NF-kappa B
  • I-kappa B Kinase
  • IKBKB protein, human
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • DDX20 protein, human
  • DEAD Box Protein 20