Sphingosine-1-Phosphate Metabolism and Its Role in the Development of Inflammatory Bowel Disease

Wollny, Tomasz; Wątek, Marzena; Durnaś, Bonita; Niemirowicz, Katarzyna; Piktel, Ewelina; Żendzian-Piotrowska, Małgorzata; Góźdż, Stanisław; Bucki, Robert

doi:10.3390/ijms18040741

Cited by 31 publications

(34 citation statements)

References 107 publications

(141 reference statements)

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“…In patients with inflammatory bowel disease (IBD), the risk of cancer is increased some 20-30-fold [52]. S1P is thought to be involved in the progression from IBD to cancer [53]. It may be that two homologous proteins (S1PL2021 and S1PL2025), which were recently reported in the pathogenic bacterium Burkholderia pseudomallei K96243, degrade host sphingolipids (SLs) via a mechanism mediated by the pyridoxal 5 0 -phosphate (PLP)dependent enzyme S1P lyase (S1PL) [54].…”

Section: Pathogenic Stimulusmentioning

confidence: 99%

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Brücher

Jamall

2019

4open

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A pathogenic (biological or chemical) stimulus is the earliest information received by a cell that can result in the disruption of homeostasis with consequent development of disease. Chronic inflammation involves many cell types with numerous cytokines and signaling pathways, the release of different components by the cells, and the crosstalk provoked by such stimuli involving subclinical chronic inflammation and is mechanistically manifold. Exosomes secrete chemicals that trigger the epithelium to produce exosome-like nanoparticles promoting chronic inflammation. Small molecules, together with various cytokines, selectively target signaling pathways inducing crosstalk that suppress apoptosis. 16S rRNA gene sequencing has become routine to provide information on the composition and abundance of bacteria found in human tissues and in reservoirs. The deregulation of autophagy with chronic stimulation of inflammation is an early phenomenon in carcinogenesis. The disruption of cell–cell integrity enables transcellular CagA migration and triggers deregulation of autophagy with the net result being chronic inflammation. The complex and insidious nature of chronic inflammation can be seen both inside and outside the cell and even with intracellular nuclear fragments such as chromatin, which itself can elicit a chronic inflammatory response within the cytoplasm and affect autophagy. The ultimate result of unresolved chronic inflammation is fibrosis, a step before tissue remodeling results in the formation of a precancerous niche (PCN). Various pathogenic stimuli associated with different neoplasms result in persistent inflammation. This ongoing disruption of homeostasis in the micromilieu of cells, tissues, and organs is an essential preamble to carcinogenesis and occurs early in that process.

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Section: Pathogenic Stimulusmentioning

confidence: 99%

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Brücher

Jamall

2019

4open

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“…Sphingosine metabolites are bioactive signaling lipids involved in many essential biological responses 1,2 . Several researchers have reported that sphingosine metabolites, such as sphingosine-1-phosphate (S1P) and phytos phingosine-1-phosphate (P1P), exert various physiological roles, including cell proliferation, differen tiation, migration, immunomodulation, metabolism, and survival [3][4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

O-cyclic phytosphingosine-1-phosphate stimulates HIF1α-dependent glycolytic reprogramming to enhance the therapeutic potential of mesenchymal stem cells

et al. 2019

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O-cyclic phytosphingosine-1-phosphate (cP1P) is a novel chemically synthesized sphingosine metabolite derived from phytosphingosine-1-phosphate. Although structurally similar to sphingosine-1-phosphate (S1P), its biological properties in stem cells remain to be reported. We investigated the effect of cP1P on the therapeutic potential of mesenchymal stem cells (MSCs) and their regulatory mechanism. We found that, under hypoxia, cP1P suppressed MSC mitochondrial dysfunction and apoptosis. Metabolic data revealed that cP1P stimulated glycolysis via the upregulation of glycolysis-related genes. cP1P-induced hypoxia-inducible factor 1 alpha (HIF1α) plays a key role for MSC glycolytic reprogramming and transplantation efficacy. The intracellular calcium-dependent PKCα/mammalian target of the rapamycin (mTOR) signaling pathway triggered by cP1P regulated HIF1α translation via S6K1, which is critical for HIF1 activation. Furthermore, the cP1P-activated mTOR pathway induced bicaudal D homolog 1 expression, leading to HIF1α nuclear translocation. In conclusion, cP1P enhances the therapeutic potential of MSC through mTOR-dependent HIF1α translation and nuclear translocation.

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“…Sphingomyelin, cholesterol, and other phospholipids are important components in the cell membrane, and their most pivotal function is acting as bioactive signaling molecules. Among them, sphingosine-1-phosphate (S1P) produced by sphingomyelin, is not only used as intracellular second messengers to regulated the cell cycle, but also binds to the specific receptors on the cell surface to modulate cell proliferation, apoptosis, invasion, migration, and adhesion molecule expression [ 12 – 14 ]. In addition, S1P can promote the survival of many cell types and simultaneously inhibit its apoptosis, and the biological effect mediated by S1P is closely correlated with tumor formation [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Triple Negative Breast Cancer Depends on Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P)/Sphingosine 1-Phosphate Receptor 3 (S1PR3)/Notch Signaling for Metastasis

et al. 2018

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BackgroundTriple negative breast cancer (TNBC) has a more aggressive recurrence. Previous reports have demonstrated that sphingosine kinase 1 (SphK1) is a crucial regulator of breast cancer progression. However, the correlation of SphK1 with clinical prognosis has been poorly investigated. Thus, we aimed to elaborate the role of SphK1 in TNBC metastasis.Material/MethodsWe first determined the level of SphK1 in breast cancer tissue samples and breast cancer cells. Furthermore, the expression of HER2 and phosphor-SphK1 (pSphK1) in human breast cancer tissue samples was determined by immunohistochemical analysis. Associations between SphK1 and clinical parameters of tumors were analyzed. The activity of SphK1 was measured by fluorescence analysis. Extracellular sphingosine-1-phosphate (S1P) was detected using an ELISA kit. Associations between SphK1 and metastasis potential were analyzed by Transwell assay.ResultsLevels of SphK1 in TNBC patients were significantly higher than levels in other patients with other breast tumors. The expression of SphK1 was positively correlated with poor overall survival (OS) and progression-free survival (PFS), as well as poor response to 5-FU and doxorubicin. The depression of SphK1 thus could repress the Notch signaling pathway, reduce migration, and invasion of TNBC cells in vivo and in vitro. Furthermore, silencing of SphK1 by Ad-SPHK1-siRNA or SphK1 inhibitor PF543 sensitized TNBCs to 5-FU and doxorubicin. Our results also indicated that SphK1 inhibition could effectively counteracts tumors metastasis via Notch signaling pathways, indicating a potentially anti-tumor strategy in TNBC.ConclusionsWe found that elevated levels of pSphK1 were positive correlation with high expression of S1P, which in turn promoted metastasis of TNBC through S1P/S1PR3/Notch signaling pathway.

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Sphingosine-1-Phosphate Metabolism and Its Role in the Development of Inflammatory Bowel Disease

Cited by 31 publications

References 107 publications

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

O-cyclic phytosphingosine-1-phosphate stimulates HIF1α-dependent glycolytic reprogramming to enhance the therapeutic potential of mesenchymal stem cells

Triple Negative Breast Cancer Depends on Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P)/Sphingosine 1-Phosphate Receptor 3 (S1PR3)/Notch Signaling for Metastasis

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