Sphingosine-1-phosphate: an enigmatic signalling lipid

Spiegel, Sarah; Milstien, Sheldon

doi:10.1038/nrm1103

Cited by 1,928 publications

(2,013 citation statements)

References 89 publications

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“…This role is facilitated by the monoamine oxidases [65]. It has long been known that ceramide accumulation leads to cell death/apoptosis, what is somewhat paradoxical though, is the fact that one of its downstream metabolites sphingosine-1-phosphate (S1P) is a growth promoter and support cell survival [66]. Indeed, S1P preincubation has been shown to prevent mortality induced by hypoxia [67,68].…”

Section: Ceramide and Reactive Oxygen Speciesmentioning

confidence: 99%

Ceramide: A common pathway for atherosclerosis?

et al. 2008

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Plasma sphingomyelin concentration is correlated with the development of atherosclerosis. It has been found to exist in significantly higher concentrations in aortic plaque. This appears to have clinical relevance as well as it has been shown to be an independent predictor of coronary artery disease. Ceramide, the backbone of sphingolipids, is the key component which affects atherosclerotic changes through its important second-messenger role. This paper sheds light on some of the current literature supporting the significance of ceramide with respect to its interactions with lipids, inflammatory cytokines, homocysteine and matrix metalloproteinases. Furthermore, the potential therapeutic implications of modulating ceramide concentrations are also discussed.

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Section: Ceramide and Reactive Oxygen Speciesmentioning

confidence: 99%

Ceramide: A common pathway for atherosclerosis?

et al. 2008

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“…The function of S1P is go through its receptors S1PRs (S1PR1‐5) which belongs to the G‐protein coupled receptor (GPCR) family 2 and each receptor, respectively, involved in cell growth, apoptosis, proliferation, angiogenesis, chemo resistance, or vascular stability 5, 13, 14, 15. It is also a chemotactic factor for immune cell trafficking 5, 16, 17 and a microenvironmental regulator for cancer development 18. The growth rate of breast cancer cells was found to be decreased in SPHK1 or SPHK2 deficient mice 19.…”

Section: Introductionmentioning

confidence: 99%

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Cheng

Liao

et al. 2018

Cancer Medicine

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Sphingosine‐1‐phosphate (S1P) is a bioactive lipid that exerts various pathophysiological functions through binding to its receptor family (S1PRs). Since first report of the breast cancer (BCA) promoting function by S1P production (through the function of sphingosine kinases) and S1P/S1PR signaling, their antagonists have never been successfully progress to clinics after three decades. Taking advantage of bioinformatics linking to gene expression to disease prognosis, we examined the impact of associated genes in BCA patients. We found high gene expressions involved in S1P anabolism suppressed disease progression of patients who are basal cell type BCA or receiving adjuvant therapy. In addition, S1PRs expression also suppressed disease progress of multiple categories of BCA patient progression. This result is contradictory to tumor promoter role of S1P/S1PRs which revealed in the literature. Further examination by directly adding S1P in BCA cells found a cell growth suppression function, which act via the expression of S1PR1. In conclusion, our study is the first evidence claiming a survival benefit function of S1P/S1PR signaling in BCA patients, which might explain the obstacle of relative antagonist apply in clinics.

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“…In addition, it has been demonstrated that substantial crosstalk exists between S1P and other proangiogenic growth factors such as VEGF, EGF, PDGF, bFGF and IL-8. For example, S1P transactivates EGF (Shida et al, 2004) and VEGF2 receptors (Spiegel and Milstien, 2003) and VEGF upregulates S1P 1 receptor expression (Igarashi et al, 2003). Also, S1P, acting via S1P 1 and the 'VEFG axis,' is required for hind-limb angiogenesis and neovascularisation (Chae et al, 2004).…”

Section: Sphingosine-1-phosphate and Tumour Angiogenesismentioning

confidence: 99%

Targeting sphingosine-1-phosphate for cancer therapy

Sabbadini

2006

Br J Cancer

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This review summarises some important new findings that implicate sphingosine-1-phosphate (S1P) as a potent tumorigenic and angiogenic agent released from cancerous tumours into the tumour microenvironment. Also explored is the novel concept that bioactive lipid signalling molecules, like S1P, can themselves be targets for rational drug design, thereby opening up an entire class of lipidomic-based therapeutics for oncology and other human diseases.

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Sphingosine-1-phosphate: an enigmatic signalling lipid

Cited by 1,928 publications

References 89 publications

Ceramide: A common pathway for atherosclerosis?

Ceramide: A common pathway for atherosclerosis?

Survival benefit of sphingosin‐1‐phosphate and receptors expressions in breast cancer patients

Targeting sphingosine-1-phosphate for cancer therapy

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