Ceramide 1-phosphate (C1P) promotes cell migration

Granado, María H.; Gangoiti, Patricia; Ouro, Alberto; Arana, Lide; González, Monika; Trueba, Miguel; Gómez-Muñoz, Antonio

doi:10.1016/j.cellsig.2008.11.003

Cited by 132 publications

(164 citation statements)

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“…Using radiolabelled C1P we have verified that S1P and LPA do not compete with C1P on binding to its receptor (Granado et al, 2009b). Thus, it can be concluded that the C1P receptor represents a novel phospholipid-binding receptor.…”

Section: Evidence For the Existence Of A Specific C1p Receptor Implimentioning

confidence: 70%

“…In addition, C1P stimulated the DNA binding activity of NF-κB via both ERK1/2 and PKB, and specific blockade of this transcription factor also resulted in complete inhibition of macrophage migration. Finally, like cell migration, activation of these signaling pathways was M a n u s c r i p t 6 blocked by pertusis toxin, further demonstrating that cell migration is induced by C1P via a G icoupled receptor, which is upstream to the MEK/ERK1/2, PI-3K/PKB and NFκB pathways (Granado et al, 2009b). Although these pathways are also involved in the mitogenic and/or antiapoptotic effects of C1P, their activation are independent of interaction with the C1P receptor, possibly because they belong to a pool of kinases that is spatially distinct to that involved in C1P-stimulated-cell migration (Gómez-Muñoz et al, 2009).…”

Section: Evidence For the Existence Of A Specific C1p Receptor Implimentioning

confidence: 84%

“…2. 1) C1P elicited cell migration (Granado et al, 2009b), whereas PCERA-1 modulated LPSinduced TNF and IL-10 production (Goldsmith et al, 2008). 2) C1P elevated ERK1/2 and JNK (but not p38) phosphorylation (Granado et al, 2009b), whereas PCERA-1 elevated p38 (but not ERK1/2 and JNK) phosphorylation ).…”

Section: Functional Comparison Of C1p and Pcera-1mentioning

confidence: 96%

“…C1P activated the NFB and PI-3K pathways (Granado et al, 2009b), whereas PCERA-1 neither significantly affected nuclear translocation of NFB (Goldsmith et al, 2008), nor activated PI-3K (Avni and Zor, unpublished).…”

Section: )mentioning

confidence: 99%

“…The number of macrophages in tissues is determined by the rates of monocyte recruitment from the bloodstream, the rates of macrophage proliferation and apoptosis, and the rate of macrophage migration and efflux. Recent studies demonstrated that exogenous addition of natural C1P to RAW264.7 macrophages caused cell migration (Granado et al, 2009b). This effect only occurred when C1P was added exogenously to the cells in culture, and was independent of the intra-cellular formation of C1P.…”

Section: Evidence For the Existence Of A Specific C1p Receptor Implimentioning

confidence: 99%

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Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

Levi

Meijler

Gómez-Muñoz

et al. 2010

Molecular and Cellular Endocrinology

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. Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1). Molecular and Cellular Endocrinology, Elsevier, 2009, 314 (2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 Ceramide-1-phosphate (C1P) is known as a second messenger regulating a multitude of processes including cell growth, apoptosis and inflammation. Exciting recent findings now suggest that C1P can stimulate macrophages migration in an extra-cellular manner via a G protein-coupled receptor (GPCR). Interestingly, a synthetic C1P analog, named phospho-ceramide analogue-1 (PCERA-1), was recently described as a potent in-vivo anti-inflammatory agent, and was suggested to act on macrophages in an extra-cellular manner via a GPCR. Here we summarize and compare the receptor-mediated as well as receptor-independent activities of natural C1P and its synthetic analog. We also provide experimental data in support of distinct C1P and PCERA-1 receptors.Page 3 of 20A c c e p t e d M a n u s c r i p t 3 IntroductionIt is well-established that sphingolipids are crucial metabolites for controlling cell and tissue homeostasis. In particular, ceramides induce cell cycle arrest and are potent inducers of apoptosis. Also, ceramides play crucial roles in the regulation of cell differentiation, and inflammation (Hannun et al., 1986;Hannun, 1994;Hannun and Obeid, 1995;Hannun, 1996;Hannun and Obeid, 2002;Kolesnick, 1994;Kolesnick, 1987;Kolesnick and Hemer, 1990;Kolesnick et al., 2000;Merrill and Jones, 1990;Merrill et al., 1997;Merrill, 2002;Spiegel and Merrill, 1996).Ceramides are generated either by de novo synthesis, or by the action of different sphingomyelinases (SMases), whose activities, enzymology, and compartmentalization have been thoroughly reviewed by others (Cremesti et al., 2002;Goni and Alonso, 2002;Kolesnick et al., 2000). A major metabolite of ceramide is ceramide-1-phosphate (C1P, Fig. 1), which is generated through direct phosphorylation of ceramide by ceramide kinase (CERK) (Bajjalieh et al., 1989;Kolesnick and Hemer, 1990). This enzyme was first shown to be confined to the microsomal fraction, but its location in the cytosol has also been reported (Mitsutake et al., 2004). Recently, Chalfant and co-workers demonstrated that CERK utilizes ceramide transported to the trans-Golgi apparatus by the ceramide transport protein (CERT). Of note, down-regulation of CERT by RNA interference resulted in strong inhibition of newly synthesized C1P, suggesting that CERT plays a critical role in C1P formation . However, this observation contrasts with that of Bornancin and...

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Section: Evidence For the Existence Of A Specific C1p Receptor Implimentioning

confidence: 70%

Section: Evidence For the Existence Of A Specific C1p Receptor Implimentioning

confidence: 84%

Section: Functional Comparison Of C1p and Pcera-1mentioning

confidence: 96%

Section: )mentioning

confidence: 99%

Section: Evidence For the Existence Of A Specific C1p Receptor Implimentioning

confidence: 99%

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Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

Levi

Meijler

Gómez-Muñoz

et al. 2010

Molecular and Cellular Endocrinology

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Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance

2021

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Cancer development is a multistep process in which cells must overcome a series of obstacles before they can become fully developed tumors. First, cells must develop the ability to proliferate unchecked. Once this is accomplished, they must be able to invade the neighboring tissue, as well as provide themselves with oxygen and nutrients. Finally, they must acquire the ability to detach from the newly formed mass in order to spread to other tissues, all the while evading an immune system that is primed for their destruction. Furthermore, increased levels of inflammation have been shown to be linked to the development of cancer, with sites of chronic inflammation being a common component of tumorigenic microenvironments. In this Review, we give an overview of the impact of sphingolipid metabolism in cancers, from initiation to metastatic dissemination, as well as discussing immune responses and resistance to treatments. We explore how sphingolipids can either help or hinder the progression of cells from a healthy phenotype to a cancerous one.

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Ceramide-1-Phosphate Regulates Migration of Multipotent Stromal Cells and Endothelial Progenitor Cells—Implications for Tissue Regeneration

et al. 2013

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Ceramide-1-phosphate (C1P) is a bioactive lipid that, in contrast to ceramide, is an anti-apoptotic molecule released from cells that are damaged and “leaky”. As reported recently, C1P promotes migration of hematopoietic cells. In the current paper, we tested the hypothesis that C1P released upon tissue damage may play an underappreciated role in chemoattraction of various types of stem cells and endothelial cells involved in tissue/organ regeneration. We show for a first time that C1P is upregulated in damaged tissues and chemoattracts BM-derived multipotent stroma cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs). Furthermore, compared to other bioactive lipids, C1P more potently chemoattracted human umbilical vein endothelial cells (HUVECs) and stimulated tube formation by these cells. C1P also promoted in vivo vascularization of Matrigel implants and stimulated secretion of stromal derived factor-1 (SDF-1) from BM-derived fibroblasts. Thus, our data demonstrate, for the first time, that C1P is a potent bioactive lipid released from damaged cells that potentially plays an important and novel role in recruitment of stem/progenitor cells to damaged organs and may promote their vascularization.

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Ceramide 1-phosphate (C1P) promotes cell migration

Cited by 132 publications

References 30 publications

Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance

Ceramide-1-Phosphate Regulates Migration of Multipotent Stromal Cells and Endothelial Progenitor Cells—Implications for Tissue Regeneration

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