The atypical sphingosine 1-phosphate variant, d16:1 S1P, mediates CTGF induction via S1P2 activation in renal cell carcinoma.
Animals
Carbon
Carcinoma, Renal Cell
/ genetics
Connective Tissue Growth Factor
/ genetics
Humans
Kidney Neoplasms
/ genetics
Lysophospholipids
/ metabolism
Mice
Receptors, Lysosphingolipid
/ genetics
Serine C-Palmitoyltransferase
Sphingolipids
Sphingosine
/ analogs & derivatives
Sphingosine-1-Phosphate Receptors
A498 cells
CTGF
RCC
S1P receptors
sphingosine 1-phosphate homologues
Journal
The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
02
02
2022
received:
30
08
2021
accepted:
22
03
2022
pubmed:
24
3
2022
medline:
23
9
2022
entrez:
23
3
2022
Statut:
ppublish
Résumé
Sphingosine 1-phosphate (S1P) is a lipid mediator with numerous biological functions. The term 'S1P' mainly refers to the sphingolipid molecule with a long-chain sphingoid base of 18 carbon atoms, d18:1 S1P. The enzyme serine palmitoyltransferase catalyses the first step of the sphingolipid de novo synthesis using palmitoyl-CoA as the main substrate. After further reaction steps, d18:1 S1P is generated. However, also stearyl-CoA or myristoyl-CoA can be utilised by the serine palmitoyltransferase, which at the end of the S1P synthesis pathway, results in the production of d20:1 S1P and d16:1 S1P respectively. We measured these S1P homologues in mice and renal tissue of patients suffering from renal cell carcinoma (RCC). Our experiments highlight the relevance of d16:1 S1P for the induction of connective tissue growth factor (CTGF) in the human renal clear cell carcinoma cell line A498 and human RCC tissue. We show that d16:1 S1P versus d18:1 and d20:1 S1P leads to the highest CTGF induction in A498 cells via S1P2 signalling and that both d16:1 S1P and CTGF levels are elevated in RCC compared to adjacent healthy tissue. Our data indicate that d16:1 S1P modulates conventional S1P signalling by acting as a more potent agonist at the S1P2 receptor than d18:1 S1P. We suggest that elevated plasma levels of d16:1 S1P might play a pro-carcinogenic role in the development of RCC via CTGF induction.
Substances chimiques
Lysophospholipids
0
Receptors, Lysosphingolipid
0
Sphingolipids
0
Sphingosine-1-Phosphate Receptors
0
Connective Tissue Growth Factor
139568-91-5
sphingosine 1-phosphate
26993-30-6
Carbon
7440-44-0
Serine C-Palmitoyltransferase
EC 2.3.1.50
Sphingosine
NGZ37HRE42
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5670-5681Informations de copyright
© 2022 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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