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Sphingolipid Metabolism in Tumor Cells

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Abstract

Sphingolipids are a diverse family of complex lipids typically composed of a sphingoid base bound to a fatty acid via amide bond. The metabolism of sphingolipids has long remained out of focus of biochemical studies. Recently, it has been attracting an increasing interest of researchers because of different and often multidirectional effects demonstrated by sphingolipids with a similar chemical structure. Sphingosine, ceramides (N-acylsphingosines), and their phosphorylated derivatives (sphingosine-1-phosphate and ceramide-1-phosphates) act as signaling molecules. Ceramides induce apoptosis and regulate stability of cell membranes and cell response to stress. Ceramides and sphingoid bases slow down anabolic and accelerate catabolic reactions, thus suppressing cell proliferation. On the contrary, their phosphorylated derivatives (ceramide-1-phosphate and sphingosine-1-phosphate) stimulate cell proliferation. Involvement of sphingolipids in the regulation of apoptosis and cell proliferation makes them critically important in tumor progression. Sphingolipid metabolism enzymes and sphingolipid receptors can be potential targets for antitumor therapy. This review describes the main pathways of sphingolipid metabolism in human cells, with special emphasis on the properties of this metabolism in tumor cells.

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Abbreviations

ARS:

arylsulfatase

Cer:

ceramide

CERase:

ceramidase

CERK:

ceramide kinase

CERS:

ceramide synthase

CST:

cerebroside sulfotransferase

CERT:

ceramide transporter

C1P:

ceramide-1-phosphate

DEGS:

dihydroceramide desaturase

dhCer:

dihydroceramide

dhS1P:

dihydrosphingosine-1-phosphate

ER:

endoplasmic reticulum

GalCer:

galactosylceramide

GALC:

galactosyl ceramidase

GalCERS:

galactosylcerebroside synthase

GluCer:

glucosylceramide

GluCERase:

glucosylceramidase

GluCERS:

glucosylcerebroside synthase

PA:

phosphatidic acid

SGPP:

sphingosine-1-phosphate phosphatase

SM:

sphingomyelin

SMase:

sphingomyelinase

SMS:

sphingomyelin synthase

Sph:

sphingosine

SPHK:

sphingosine kinase

S1P:

sphingosine-1-phosphate

S1PL:

sphingosine-1-phosphate lyase

TNF-α:

tumor necrosis factor α

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Funding

The study was carried out within the framework of the State Task of the RUDN University of the Ministry of Science and Higher Education no. 075-01551-23-00 (FSSF-2023-0006).

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  1. People’s Friendship University of Russia (RUDN University), 117198, Moscow, Russia

    Vadim S. Pokrovsky, Veronika I. Ivanova-Radkevich & Olga M. Kuznetsova

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V.S.P. conceived and supervised the study and edited the manuscript; V.I.I.-R. and O.M.K. wrote and edited the manuscript.

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Pokrovsky, V.S., Ivanova-Radkevich, V.I. & Kuznetsova, O.M. Sphingolipid Metabolism in Tumor Cells. Biochemistry Moscow 88, 847–866 (2023). https://doi.org/10.1134/S0006297923070015

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