The atypical sphingosine 1-phosphate variant, d16:1 S1P, mediates CTGF induction via S1P2 activation in renal cell carcinoma
- 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.
Author: | Melanie GlückGND, Alexander Koch, Robert BrunkhorstGND, Nerea Ferreiros BouzasORCiDGND, Sandra TrautmannGND, Liliana SchäferORCiD, Waltraud PfeilschifterORCiDGND, Josef PfeilschifterGND, Rajkumar VutukuriORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-773811 |
DOI: | https://doi.org/10.1111/febs.16446 |
ISSN: | 1742-4658 |
Parent Title (English): | The FEBS Journal |
Publisher: | Wiley-Blackwell |
Place of publication: | Oxford [u.a.] |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/03/23 |
Date of first Publication: | 2022/03/23 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/10/05 |
Tag: | A498 cells; CTGF; RCC; S1P receptors; sphingosine 1-phosphate homologues |
Volume: | 289.2022 |
Issue: | 18 |
Page Number: | 12 |
First Page: | 5670 |
Last Page: | 5681 |
Note: | This work was supported by the German Research Foundation (SFB 1039) and Uniscientia Foundation (Vaduz) grants. |
Note: | The data that support the findings of this study are available from the corresponding author, RV, upon reasonable request. |
HeBIS-PPN: | 513641904 |
Institutes: | Medizin |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften |
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie | |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |