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

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...

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Bibliographic Details
Published in:Cancer cell Vol. 24; no. 2; p. 229
Main Authors: Masiero, Massimo, Simões, Filipa Costa, Han, Hee Dong, Snell, Cameron, Peterkin, Tessa, Bridges, Esther, Mangala, Lingegowda S, Wu, Sherry Yen-Yao, Pradeep, Sunila, Li, Demin, Han, Cheng, Dalton, Heather, Lopez-Berestein, Gabriel, Tuynman, Jurriaan B, Mortensen, Neil, Li, Ji-Liang, Patient, Roger, Sood, Anil K, Banham, Alison H, Harris, Adrian L, Buffa, Francesca M
Format: Journal Article
Language:English
Published: United States 12.08.2013
Subjects:
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
ISSN:1878-3686, 1878-3686
Online Access:Get more information
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Summary: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.
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ISSN:1878-3686
1878-3686
DOI:10.1016/j.ccr.2013.06.004