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Review
. 2022 Apr 19;14(9):2051.
doi: 10.3390/cancers14092051.

Sphingolipids and Lymphomas: A Double-Edged Sword

Alfredo Pherez-Farah  1 , Rosa Del Carmen López-Sánchez  1 , Luis Mario Villela-Martínez  2   3   4 , Rocío Ortiz-López  1 , Brady E Beltrán  5   6 , José Ascención Hernández-Hernández  1
Affiliations
Review

Sphingolipids and Lymphomas: A Double-Edged Sword

Alfredo Pherez-Farah et al. Cancers (Basel). .

Abstract

Lymphomas are a highly heterogeneous group of hematological neoplasms. Given their ethiopathogenic complexity, their classification and management can become difficult tasks; therefore, new approaches are continuously being sought. Metabolic reprogramming at the lipid level is a hot topic in cancer research, and sphingolipidomics has gained particular focus in this area due to the bioactive nature of molecules such as sphingoid bases, sphingosine-1-phosphate, ceramides, sphingomyelin, cerebrosides, globosides, and gangliosides. Sphingolipid metabolism has become especially exciting because they are involved in virtually every cellular process through an extremely intricate metabolic web; in fact, no two sphingolipids share the same fate. Unsurprisingly, a disruption at this level is a recurrent mechanism in lymphomagenesis, dissemination, and chemoresistance, which means potential biomarkers and therapeutical _targets might be hiding within these pathways. Many comprehensive reviews describing their role in cancer exist, but because most research has been conducted in solid malignancies, evidence in lymphomagenesis is somewhat limited. In this review, we summarize key aspects of sphingolipid biochemistry and discuss their known impact in cancer biology, with a particular focus on lymphomas and possible therapeutical strategies against them.

Keywords: cancer; lipid metabolism; lipidomics; lymphoma; sphingolipids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of sphingolipid metabolism. SPT: serine palmitoyltransferase; CS: ceramide synthase; DES: dihydroceramide desaturase; CDase: ceramidase; SK: sphingosine kinase; S1Pase: sphingosine-1-phosphate-phosphatase; S1P-lyase: sphingosine-1-phosphate lyase; S1PR1: sphingosine-1-phosphate receptor 1; CK: ceramide kinase; CPase: ceramide-1-phosphate-phosphatase; SMS: sphingomyelin synthase; SMase: sphingomyelinase; PC: phosphocholine; DAG: diacylglycerol; GluCerS: glucosylceramide synthase; LacCerS: lactosylceramide synthase; HEXs: hexosaminidases; NEUs: neuraminidases; GTFs: glycosyltransferases; SATs: sialyltransferases; GM2A: ganglioside activator protein; SAPs: sphingolipid activator proteins (saposins); GlucCDase: glucosylceramidase; GalCerS: galactosylceramide synthase; GalCDase: galactosylceramidase. Considerations: Orange arrows depict de novo pathway. Purple arrows depict salvage pathway. Red arrows depict SM cycle. Blue arrows depict GSL metabolism. CDase and SMase have acid, alkaline, and neutral isotypes, depending on the subcellular compartment. Multiple intracellular transporters (CERT, FAPP2, CPTP, SPNS2, Mfsd2d, GLTP) move newly synthesized sphingolipids across subcellular compartments to ensure proper distribution.
Figure 2
Figure 2
Summary of antineoplastic vs lymphomagenic sphingolipids. * Synthetic; S1P: Sphingosine-1-Phosphate; S1PR-2: Sphingosine-1-Phosphate Receptor 2; α-GalCer: α-galactosylceramide; SM: sphingomyelin; β-GlcCer: β-glucosylceramide; GM3: monosialodihexosylganglioside; Gb3: globotriaosylceramide.
Figure 3
Figure 3
Potential therapeutical with published evidence against lymphomas. Green boxes represent enzymatic inducers and red boxers represent enzymatic inhibitors. SPT: serine palmitoyltransferase; CS: ceramide synthase; DES: dihydroceramide desaturase; CDase: ceramidase; SK: sphingosine kinase; S1Pase: sphingosine-1-phosphate-phosphatase; S1P-lyase: sphingosine-1-phosphate lyase; S1PR1: sphingosine-1-phosphate receptor 1; CK: ceramide kinase; CPase: ceramide-1-phosphate-phosphatase; SMS: sphingomyelin synthase; SMase: sphingomyelinase; PC: phosphocholine; DAG: diacylglycerol; GluCerS: glucosylceramide synthase; LacCerS: lactosylceramide synthase; HEXs: hexosaminidases; NEUs: neuraminidases; GTFs: glycosyltransferases; SATs: sialyltransferases; GlucCDase: glucosylceramidase; GalCerS: galactosylceramide synthase; GalCDase: galactosylceramidase; 4-HPRT: N-(4-hydroxypheny) retinamide (fenretinide); R(+)-MA: R(+)-methanandamide; PPMP: 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol; D609: Tricyclodecan-9-yl-xanthogenate; NOE: N-oleoylethanolamine; Man-A: Manomycin A; C11AG: undecylidene-aminoguanidine.
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References

    1. Hannun Y.A., Obeid L.M. Sphingolipids and their metabolism in physiology and disease. Nat. Rev. Mol. Cell Biol. 2018;19:175–191. doi: 10.1038/nrm.2017.107. - DOI - PMC - PubMed
    1. Bultman S.J. Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer. Mol. Nutr. Food Res. 2017;61:1500902. doi: 10.1002/mnfr.201500902. - DOI - PMC - PubMed
    1. Bédard A.-S.V., Hien E.D., Lafontaine D.A. Riboswitch regulation mechanisms: RNA, metabolites and regulatory proteins. Biochim. et Biophys. Acta. 2020;1863:194501. doi: 10.1016/j.bbagrm.2020.194501. - DOI - PubMed
    1. Garcia-Bermudez J., Baudrier L., Bayraktar E., Shen Y., La K., Guarecuco R., Yucel B., Fiore D., Tavora B., Freinkman E., et al. Squalene accumulation in cholesterol auxotrophic lymphomas prevents oxidative cell death. Nature. 2019;567:118–122. doi: 10.1038/s41586-019-0945-5. - DOI - PMC - PubMed
    1. Haque S., Yan X.J., Rosen L., McCormick S., Chiorazzi N., Mongini P.K.A. Effects of prostaglandin E2on p53 mRNA transcription and p53 mutagenesis during T-cell-independent human B-cell clonal expansion. FASEB J. 2014;28:627–643. doi: 10.1096/fj.13-237792. - DOI - PMC - PubMed

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