title: A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis.
abstract: 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.
authors.affiliation: Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK.
authors.forename: Massimo
authors.initials: M
authors.lastname: Masiero
authors.forename: Filipa Costa
authors.initials: FC
authors.lastname: Simões
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.forename: Cameron
authors.initials: C
authors.lastname: Snell
authors.forename: Tessa
authors.initials: T
authors.lastname: Peterkin
authors.forename: Esther
authors.initials: E
authors.lastname: Bridges
authors.forename: Lingegowda S
authors.initials: LS
authors.lastname: Mangala
authors.forename: Sherry Yen-Yao
authors.initials: SY
authors.lastname: Wu
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.forename: Demin
authors.initials: D
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Han
authors.forename: Heather
authors.initials: H
authors.lastname: Dalton
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: Jurriaan B
authors.initials: JB
authors.lastname: Tuynman
authors.forename: Neil
authors.initials: N
authors.lastname: Mortensen
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Li
authors.forename: Roger
authors.initials: R
authors.lastname: Patient
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Alison H
authors.initials: AH
authors.lastname: Banham
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Harris
authors.forename: Francesca M
authors.initials: FM
authors.lastname: Buffa
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C428324:ADGRL4 protein, human; D043562:Receptors, G-Protein-Coupled