S1P is a small bioactive lipid which exerts its effects following binding to a family of five G protein-coupled receptors, known as S1P. Following receptor activation, multiple signalling cascades are activated, allowing S1P to regulate a range of cellular processes, such as proliferation, apoptosis, migration and angiogenesis. There is strong evidence implicating the involvement of S1P receptors (S1PRs) in cancer progression and the oncogenic effects of S1P can result from alterations in the expression of one or more of the S1PRs and/or the enzymes that regulate the levels of S1P. However, cooperativity between the individual S1PRs, functional interactions with receptor tyrosine kinases and the sub-cellular localisation of the S1PRs within tumour cells also appear to play a role in mediating the effects of S1PR signalling during carcinogenesis. Here we review what is known regarding the role of individual S1PRs in cancer and discuss the recent evidence to suggest cross-talk between the S1PRs and other cellular signalling pathways in cancer. We will also discuss the therapeutic potential of targeting the S1PRs and their downstream signalling pathways for the treatment of cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cellsig.2017.03.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Broad and diverse roles of sphingosine-1-phosphate/sphingosine-1-phosphate receptors in the prostate.
iScience
December 2024
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Article Synopsis
- Benign prostatic hyperplasia (BPH) is a common issue in older males, but how it develops is still not fully understood, prompting research into the role of sphingosine-1-phosphate (S1P) and its receptors (S1PRs) in the prostate.
- The study found that S1P and its receptors are highly expressed in the prostate, and S1PR1, S1PR2, and S1PR3 are involved in promoting cell growth, muscle contraction, and reducing inflammation via various cellular pathways.
- Treatment with S1P and specific receptor agonists led to prostate enlargement in rats, while antagonists of S1PR1 and S1PR3 reduced BPH symptoms
Effect of Hepatic Lipid Overload on Accelerated Hepatocyte Proliferation Promoted by HGF Expression via the SphK1/S1PR2 Pathway in MCD-diet Mouse Partial Hepatectomy.
Acta Histochem Cytochem
October 2024
Department of Anatomy, Histochemistry and Cell Biology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a major health problem worldwide. Liver regeneration is crucial for restoring liver function, and is regulated by extraordinary complex process, involving numerous factors under both physiologic and pathologic conditions. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid synthesized by sphingosine kinase 1 (SphK1), plays an important role in liver function through S1P receptors (S1PRs)-expressing cells.
View Article and Find Full Text PDFRole of Sphingosine-1-Phosphate Signaling Pathway in Pancreatic Diseases.
Int J Mol Sci
October 2024
West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Sphingosine-1-phosphate (S1P) is a sphingolipid metabolic product produced via the phosphorylation of sphingosine by sphingosine kinases (SPHKs), serving as a powerful modulator of various cellular processes through its interaction with S1P receptors (S1PRs). Currently, this incompletely understood mechanism in pancreatic diseases including pancreatitis and pancreatic cancer, largely limits therapeutic options for these disorders. Recent evidence indicates that S1P significantly contributes to pancreatic diseases by modulating inflammation, promoting pyroptosis in pancreatic acinar cells, regulating the activation of pancreatic stellate cells, and affecting organelle functions in pancreatic cancer cells.
View Article and Find Full Text PDFTargeting sphingosine 1-phosphate and sphingosine kinases in pancreatic cancer: mechanisms and therapeutic potential.
Cancer Cell Int
October 2024
College of Pharmacy, Mokpo National University, Joennam, 58554, South Korea.
Pancreatic cancer is known to be the most lethal cancer. Fewer new treatments are being developed for pancreatic cancer as compared to other cancers. The bioactive lipid S1P, which is mainly regulated by sphingosine kinase 1 (SK1) and sphingosine kinase 2 (SK2) enzymes, plays significant roles in pancreatic cancer initiation and exacerbation.
View Article and Find Full Text PDFSPHK1 promotes bladder cancer metastasis via PD-L2/c-Src/FAK signaling cascade.
Cell Death Dis
September 2024
Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
SPHK1 (sphingosine kinase type 1) is characterized as a rate-limiting enzyme in sphingolipid metabolism to phosphorylate sphingosine into sphingosine-1-phosphate (S1P) that can bind to S1P receptors (S1PRs) to initiate several signal transductions leading to cell proliferation and survival of normal cell. Many studies have indicated that SPHK1 is involved in several types of cancer development, however, a little is known in bladder cancer. The TCGA database analysis was utilized for analyzing the clinical relevance of SPHK1 in bladder cancer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!