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Biomap#81

Title: Ceramide, sphingosine and S1P biology
 
Legend: Sphingolipids not only function as structural components of cell membranes but also act as signaling molecules to regulate fundamental cellular responses [1]. Ceramide, a sphingosine-based lipid molecule, is a key regulator of a wide spectrum of biological processes such as cellular differentiation, proliferation, apoptosis and senescence. In particular, the balance between ceramide and sphingosine 1-phosphate (S1P) plays a significant role in the cell "decision" to either undergo apoptosis or proliferate, two key events in tumor development and growth, with ceramide possessing proapoptotic capacity in many cell types and S1P acting as an antiapoptotic factor that promotes also cell proliferation [2]. Therefore, tipping the balance in favor of ceramide is a promising rational approach to effectively fight cancer [3], including melanoma [4]. REFERENCES: [1] Hannun YA, Nat Rev Mol Cell Biol 2008, 9(2):139-50. [2] Savtchouk IA, Sci STKE 2007, 394:jc1. [3] Huwiler A, Curr Pharm Des 2006, 12:4625-35. [4] Tran MA, Clin Cancer Res 2008, 14:3571-81. CITED MOLECULES: 14-3-3 (adaptor protein), 3-Ketosphinganine, ABCC1 (ATP binding cassette C1), AD2646 (drug), AIF (apoptosis inducing factor), Akt (protein kinase B, PKB), APAF1 (apoptotic peptidase activating factor 1, CED4), aSMase (acid sphingomyelinase, sphingomyelin phosphodiesterase 1, SMPD1), B13 (drug), Bad (BCL2-associated agonist of cell death), Bak (BCL2-antagonist/killer 1), Bax (BCL2-associated X protein), Bcl-2 (B-cell CLL/lymphoma 2), Bcl-xL (BCL2-like 1), BID (BH3 interacting domain [death agonist]), Bim (BCL2L11, BCL2-like 11 apoptosis facilitator), CAD (caspase activated DNase), Caspase-3, Caspase-8, Caspase-9, Cathepsin D, CDK2 (cyclin dependent kinase 2), Cer-1P (ceramide 1 phosphate), Ceramidase, Ceramide, CERK (ceramide kinase), CerS (LAG1 homolog, ceramide synthase, LASS), CFTR (cystic fibrosis transmembrane conductance regulator), Cytochr-C (Cytochrome-C), Cytokine, D-e-MAPP (drug), Desaturase, DHCer (dihydroceramide), DMS (dimethylsphingosine, drug), EndoG (endonuclease G), ERK (extracellular signal regulated kinase, MAPK), F-12509a (drug), FAN (factor associated with N-SMase, NSMAF), Fumonisin B1 (drug), Galactosylcerebroside, GALC (galactosylceramidase), GBA (beta glucosidase, GLCM), GCS (ceramide glucosyltransferase, CEGT), Glucosylceramide, HTRA2 (high temperature requirement protein A2, serine protease), IAP (inhibitor of apoptosis), ICAD (inhibitor of CAD, DFFA), KDSR (3-ketodihydrosphingosine reductase, FVT-1), KSR (kinase suppressor of RAS, scaffold protein), LCL204 (drug), Livin (BIRC7), MEK (MAP2K), Myriocin (drug), NB-DNJ (N-butyl-deoxynojirimycin), NFkB (nuclear factor kappa B), NOE (N-oleoylethanolamine, drug), Noxa (PMAIP1, BH3 only protein), nSMase (neutral sphingomyelinase, sphingomyelin phosphodiesterase 2, SMPD2), p21, p53, Palmitate, Palmithaldehyde, PAR4 (Prostate apoptosis response 4 protein, PAWR), PDMP (drug), P-ethanolamine, PI3K (phosphatidyl inositol 3 kinase), PKC (protein kinase C), PKC delta, PKC zeta, PLA2 (phospholipase A2), PLC (phospholipase C), PLD (phospholipase D), PP1 (protein phosphatase 1), PP2A (protein phosphatase 2A), PPMP (drug) pRB (retinoblastoma protein, RB1), PSC833 (drug), Puma (p53 upregulated modulator of apoptosis, BBC3), RAC (Ras-related C3 botulinum toxin substrate [rho family] small GTP binding protein), RAF (v-Raf oncogene homolog), RAS (v-Ras oncogene homolog), ROS (reactive oxygen species), Rottlerin (drug), S1P (sphingosine 1 phosphate), S1PR (sphingosine 1 phosphate receptor [G protein coupled receptor, GPCR]), SDK1 (sphingosine dependent kinase 1), SGMS (sphingomyelin synthase, SMS), SGPL (sphingosine 1 phosphate lyase, SGPL), SGPP (sphingosine-1-phosphate phosphatase, SGPP), SMAC (second mitochondria-derived activator of caspase, DIABLO), SMase (sphingomyelinase), Sphinganine, Sphingomyelin, Sphingosine, SPHK (sphingosine kinase), SPT (serine palmitoyltransferase), Survivin (BIRC5), UVR (ultraviolet radiation), XIAP (X-linked inhibitor of apoptosis). Figure #81
Author: Antonio Cuadrado, University of Madrid, Spain, antonio.cuadrado@uam.es (October 2008). Thierry Levade, INSERM, Toulouse, France, thierry.levade@inserm.fr (November 2008)

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