TY  - JOUR
A1  - Glück, Melanie
A1  - Koch, Alexander
A1  - Brunkhorst, Robert
A1  - Ferreiros Bouzas, Nerea
A1  - Trautmann, Sandra
A1  - Schäfer, Liliana
A1  - Pfeilschifter, Waltraud
A1  - Pfeilschifter, Josef
A1  - Vutukuri, Rajkumar
T1  - The atypical sphingosine 1-phosphate variant, d16:1 S1P, mediates CTGF induction via S1P2 activation in renal cell carcinoma
T2  - The FEBS Journal
N2  - 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.
KW  - A498 cells
KW  - CTGF
KW  - RCC
KW  - S1P receptors
KW  - sphingosine 1-phosphate homologues
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77381
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-773811
SN  - 1742-4658
N1  - This work was supported by the German Research Foundation (SFB 1039) and Uniscientia Foundation (Vaduz) grants.
N1  - The data that support the findings of this study are available from the corresponding author, RV, upon reasonable request.
VL  - 289.2022
IS  - 18
SP  - 5670
EP  - 5681
PB  - Wiley-Blackwell
CY  - Oxford [u.a.]
ER  -