Multi-organ Site Metastatic Reactivation Mediated by Non-canonical Discoidin Domain Receptor 1 Signaling Academic Article uri icon


MeSH Major

  • Breast Neoplasms
  • Discoidin Domain Receptor 1
  • Neoplasm Metastasis
  • Signal Transduction


  • Genetic screening identifies the atypical tetraspanin TM4SF1 as a strong mediator of metastatic reactivation of breast cancer. Intriguingly, TM4SF1 couples the collagen receptor tyrosine kinase DDR1 to the cortical adaptor syntenin 2 and, hence, to PKCα. The latter kinase phosphorylates and activates JAK2, leading to the activation of STAT3. This non-canonical mechanism of signaling induces the expression of SOX2 and NANOG; sustains the manifestation of cancer stem cell traits; and drives metastatic reactivation in the lung, bone, and brain. Bioinformatic analyses and pathological studies corroborate the clinical relevance of these findings. We conclude that non-canonical DDR1 signaling enables breast cancer cells to exploit the ubiquitous interstitial matrix component collagen I to undergo metastatic reactivation in multiple target organs.

publication date

  • June 30, 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC4980842

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2016.06.009

PubMed ID

  • 27368100

Additional Document Info

start page

  • 47

end page

  • 62


  • 166


  • 1