Role of the Sphingosine-1-Phosphate Receptor EDG-1 in PDGF-Induced Cell Motility

Hobson, John P.; Rosenfeldt, Hans; Barak, Larry S.; Olivera, Ana; Poulton, Samantha; Caron, Marc G.; Milstien, Sheldon; Spiegel, Sarah

doi:10.1126/science.1057559

Cited by 408 publications

(324 citation statements)

References 19 publications

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“…Activated GPCRs can induce actin cytoskeleton reorganization to form lamellipodia, which is the flattened F-actin-rich leading edge of migrating cells (Hobson et al, 2001). The formation of lamellipodia is a key process of cell migration and has been observed in MDA-MB-231 cells (Yamada et al, 2009).…”

Section: Pristimerin Inhibits the Lamellipodia Formation In Mda-mb-23mentioning

confidence: 99%

Pristimerin Inhibits Breast Cancer Cell Migration by Up-regulating Regulator of G Protein Signaling 4 Expression

Mu¹,

Shi²,

Sun³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Background/Aim: Pristimerin isolated from Celastrus and Maytenus spp can inhibit proteasome activity. However, whether pristimerin can modulate cancer metastasis is unknown. Methods: The impacts of pristimerin on the purified and intracellular chymotrypsin proteasomal activity, the levels of regulator of G protein signaling 4 (RGS 4) expression and breast cancer cell lamellipodia formation, and the migration and invasion were determined by enzymatic, Western blot, immunofluorescent, and transwell assays, respectively. Results: We found that pristimerin inhibited human chymotrypsin proteasomal activity in MDA-MB-231 cells in a dose-dependent manner. Pristimerin also inhibited breast cancer cell lamellipodia formation, migration, and invasion in vitro by up-regulating RGS4 expression. Thus, knockdown of RGS4 attenuated pristimerin-mediated inhibition of breast cancer cell migration and invasion. Furthermore, pristimerin inhibited growth and invasion of implanted breast tumors in mice. Conclusion: Pristmerin inhibits proteasomal activity and increases the levels of RGS4, inhibiting the migration and invasion of breast cancer cells.

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Section: Pristimerin Inhibits the Lamellipodia Formation In Mda-mb-23mentioning

confidence: 99%

Pristimerin Inhibits Breast Cancer Cell Migration by Up-regulating Regulator of G Protein Signaling 4 Expression

Mu¹,

Shi²,

Sun³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…6 PDGF has also been shown to activate S1PR 1 , as revealed by phosphorylation of the latter and its interaction with ␤-arrestin, thus providing a new example of cross-communication between a tyrosine kinase receptor (the PDGF receptor) and a GPCR (S1PR 1 ). 47 It is thus thought that the accumulation of S1P triggered by the PDGF-induced stimulation of SPHK results in the activation of S1PR 1 and of downstream signaling events important for cell locomotion. 47 Mice lacking the B chain of PDGF or the receptor for PDGF-BB manifest a phenotype similar to that of the S1PR 1 knockout mice; namely, embryonic death as a result of incomplete vasculogenesis.…”

Section: Functions Of S1pmentioning

confidence: 99%

“…47 It is thus thought that the accumulation of S1P triggered by the PDGF-induced stimulation of SPHK results in the activation of S1PR 1 and of downstream signaling events important for cell locomotion. 47 Mice lacking the B chain of PDGF or the receptor for PDGF-BB manifest a phenotype similar to that of the S1PR 1 knockout mice; namely, embryonic death as a result of incomplete vasculogenesis. 48,49 The observation that S1PR 1 plays a critical role in directed cell motility thus unveils the underlying mechanism by which S1P acts as a regulator of angiogenesis.…”

Section: Functions Of S1pmentioning

confidence: 99%

“…S1PR 1 is also essential for cell migration toward a source of PDGF. 47 PDGF activates SPHK and thereby increases the intracellular concentration of S1P in a variety of cell types. 6 PDGF has also been shown to activate S1PR 1 , as revealed by phosphorylation of the latter and its interaction with ␤-arrestin, thus providing a new example of cross-communication between a tyrosine kinase receptor (the PDGF receptor) and a GPCR (S1PR 1 ).…”

Section: Functions Of S1pmentioning

confidence: 99%

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Sphingosine 1-phosphate as a therapeutic agent

2002

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The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P), formed by activation of sphingosine kinase in response to diverse stimuli, is an important lipid mediator that has novel dual actions -both inside and outside of cells. S1P is the ligand for a family of five G protein-coupled receptors. Activation of these GPCRs by S1P or dihydro-S1P regulates diverse processes, including cell migration, angiogenesis, vascular maturation, heart development, and neurite retraction. There is also abundant evidence that S1P can function as a second messenger important for regulation of calcium homeostasis, cell growth, and suppression of apoptosis. In many cases, the intracellular level of S1P and ceramide, another important sphingolipid metabolite associated with cell death and cell growth arrest, coordinately determine cell fate. Changes in S1P and ceramide have been implicated in a number of pathological conditions in which apoptosis plays an important role. Importantly, radiation-induced oocyte loss in adult female mice, the event that drives premature ovarian failure and infertility in female cancer patients, was completely prevented by in vivo therapy with S1P. Understanding the biosynthesis, metabolism and functions of S1P can uncover new targets for the pharmaceutical and therapeutic applications of S1P.

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“…Conversely, inhibition of SphK has been shown to suppress tumor growth (40). Moreover, S1P regulates angiogenesis during tumor progression in an autocrine or paracrine manner (41)(42). Thus, it is considered that SphK regulates tumor growth and can act as an oncogene.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and evaluation of sphingoid analogs as inhibitors of sphingosine kinases

Kim

Inagaki

et al. 2005

Bioorganic & Medicinal Chemistry

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Sphingosine 1-phosphate (S1P), a product of sphingosine kinases (SphK), mediates diverse biological processes such as cell differentiation, proliferation, motility and apoptosis. In an effort to search and identify specific inhibitors of human SphK, the inhibitory effects of synthetic sphingoid analogs on kinase activity were examined.Among the analogs tested, we found two, SG12 and SG14, that have specific inhibitory effects on hSphK2. N,N-Dimethylsphingosine (DMS), a well known SphK inhibitor, displayed inhibitory effects for both SphK1 and SphK2, as well as protein kinase C. In contrast, SG12 and SG14 exhibited selective inhibitory effects on hSphK2. Furthermore, SG14 did not affect PKC. In isolated platelets, SG14 blocked the conversion of sphingosine into sphingosine 1-phosphate significantly. This is the first report on the identification of a hSphK2-specific inhibitor, which may provide a useful tool for studying the biological functions of hSphK2.2

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Role of the Sphingosine-1-Phosphate Receptor EDG-1 in PDGF-Induced Cell Motility

Cited by 408 publications

References 19 publications

Pristimerin Inhibits Breast Cancer Cell Migration by Up-regulating Regulator of G Protein Signaling 4 Expression

Pristimerin Inhibits Breast Cancer Cell Migration by Up-regulating Regulator of G Protein Signaling 4 Expression

Sphingosine 1-phosphate as a therapeutic agent

Synthesis and evaluation of sphingoid analogs as inhibitors of sphingosine kinases

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