A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis

Cancer Cell. 2013 Aug 12;24(2):229-41. doi: 10.1016/j.ccr.2013.06.004. Epub 2013 Jul 18.


Limited clinical benefits derived from anti-VEGF therapy have driven the identification of new targets involved in tumor angiogenesis. Here, we report an integrative meta-analysis to define the transcriptional program underlying angiogenesis in human cancer. This approach identified ELTD1, an orphan G-protein-coupled receptor whose expression is induced by VEGF/bFGF and repressed by DLL4 signaling. Extensive analysis of multiple cancer types demonstrates significant upregulation of ELTD1 in tumor-associated endothelial cells, with a higher expression correlating with favorable prognosis. Importantly, ELTD1 silencing impairs endothelial sprouting and vessel formation in vitro and in vivo, drastically reducing tumor growth and greatly improving survival. Collectively, these results provide insight into the regulation of tumor angiogenesis and highlight ELTD1 as key player in blood vessel formation.

Publication types

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

MeSH terms

  • Animals
  • Cell Growth Processes / physiology
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Female
  • Genetic Predisposition to Disease
  • HCT116 Cells
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms / blood supply*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction


  • ADGRL4 protein, human
  • Receptors, G-Protein-Coupled

Associated data

  • GEO/GSE37956
  • GEO/GSE3922
  • GEO/GSE39223
  • GEO/GSE39413