ADGRL4/ELTD1 Silencing in Endothelial Cells Induces ACLY and SLC25A1 and Alters the Cellular Metabolic Profile.
ADGRL4/ELTD1
adhesion GPCR
metabolomics
Journal
Metabolites
ISSN: 2218-1989
Titre abrégé: Metabolites
Pays: Switzerland
ID NLM: 101578790
Informations de publication
Date de publication:
25 Nov 2019
25 Nov 2019
Historique:
received:
25
10
2019
revised:
19
11
2019
accepted:
21
11
2019
entrez:
29
11
2019
pubmed:
30
11
2019
medline:
30
11
2019
Statut:
epublish
Résumé
Adhesion G Protein-Coupled Receptor L4 (ADGRL4/ELTD1) is an endothelial cell adhesion G protein-coupled receptor (aGPCR) which regulates physiological and tumour angiogenesis, providing an attractive target for anti-cancer therapeutics. To date, ADGRL4/ELTD1's full role and mechanism of function within endothelial biology remains unknown, as do its ligand(s). In this study, ADGRL4/ELTD1 silencing, using two independent small interfering RNAs (siRNAs), was performed in human umbilical vein endothelial cells (HUVECS) followed by transcriptional profiling, target gene validation, and metabolomics using liquid chromatography-mass spectrometry in order to better characterise ADGRL4/ELTD1's role in endothelial cell biology. We show that ADGRL4/ELTD1 silencing induced expression of the cytoplasmic metabolic regulator ATP Citrate Lyase (ACLY) and the mitochondria-to-cytoplasm citrate transporter Solute Carrier Family 25 Member 1 (SLC25A1) but had no apparent effect on pathways downstream of ACLY (fatty acid and cholesterol synthesis or acetylation). Silencing induced KIT expression and affected the Notch signalling pathway, upregulating Delta Like Canonical Notch Ligand 4 (DLL4) and suppressing Jagged Canonical Notch Ligand 1 (
Identifiants
pubmed: 31775252
pii: metabo9120287
doi: 10.3390/metabo9120287
pmc: PMC6950702
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Cancer Research UK
ID : 10702
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C602/A18974
Pays : United Kingdom
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