Discoidin domain receptor 1 is associated with poor prognosis of non-small cell lung cancer and promotes cell invasion via epithelial-to-mesenchymal transition

Med Oncol. 2013;30(3):626. doi: 10.1007/s12032-013-0626-4. Epub 2013 Jun 13.


Discoidin domain receptors (DDRs) are a novel class of receptor tyrosine kinases that respond to several collagens and facilitate cell adhesion. DDR1 is highly expressed in a variety of human cancers, and it is clear that DDR1 is primarily expressed in epithelial cells including lung, colon and brain. Moreover, DDR1 expression can be stimulated by collagen types I, II, III, IV, V, VIII and XI, and aberrant signaling induced by DDR1 dysregulated expression is involved in various steps of tumorigenesis. However, the molecular mechanism underlying the role of DDR1 in cancer development is not well documented. In this study, we found that the expression of DDR1 is upregulated in non-small cell lung cancer (NSCLC) tissues and cells when compared with counterpart normal tissues and cells. Furthermore, collagen I could induce DDR1 expression, and activated DDR1 promoted NSCLC cell migration and invasion, while knockdown of DDR1 by transfection with siRNA resulted in a significant decrease in cell migrativeness and invasiveness. Enhanced DDR1 expression mediated by collagen I could activate MMP-2, N-cadherin and vimentin expression, but reduce E-cadherin expression; however, inhibition of DDR1 expression could suppress MMP-2, N-cadherin and vimentin expression and induce E-cadherin activation. In conclusion, our findings indicated that upregulation of DDR1 induced by collagen I may contribute to the development and progression of NSCLC and this effect may be associated with increased invasiveness, at least in part, via promoting epithelial-to-mesenchymal transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Collagen Type I / genetics
  • Discoidin Domain Receptor 1
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology*
  • Prognosis
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Up-Regulation / genetics
  • Vimentin / genetics


  • Cadherins
  • Collagen Type I
  • Vimentin
  • DDR1 protein, human
  • Discoidin Domain Receptor 1
  • Receptor Protein-Tyrosine Kinases
  • Matrix Metalloproteinase 2