Sphingolipid-Transporting Proteins As Cancer Therapeutic Targets

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Jul 24

PMID 31330821

Citations 15

Authors

Doaa Samaha

Housam H Hamdo

Max Wilde

Kevin Prause

Christoph Arenz

Affiliations

Soon will be listed here.

Abstract

The understanding of the role of sphingolipid metabolism in cancer has tremendously increased in the past ten years. Many tumors are characterized by imbalances in sphingolipid metabolism. In many cases, disorders of sphingolipid metabolism are also likely to cause or at least promote cancer. In this review, sphingolipid transport proteins and the processes catalyzed by them are regarded as essential components of sphingolipid metabolism. There is much to suggest that these processes are often rate-limiting steps for metabolism of individual sphingolipid species and thus represent potential target structures for pharmaceutical anticancer research. Here, we summarize empirical and biochemical data on different proteins with key roles in sphingolipid transport and their potential role in cancer.

Citing Articles

Sorting of complex sphingolipids within the cellular endomembrane systems.

Svistunov V, Ehrmann K, Lencer W, Schmieder S Front Cell Dev Biol. 2025; 12:1490870.

PMID: 40078962 PMC: 11897003. DOI: 10.3389/fcell.2024.1490870.

Dynamic metabolic modeling of ATP allocation during viral infection.

Lu A, Dukovski I, Segre D bioRxiv. 2024; .

PMID: 39605584 PMC: 11601281. DOI: 10.1101/2024.11.12.623198.

Sphingolipids in prostate cancer prognosis: integrating single-cell and bulk sequencing.

Zhou S, Sun L, Mao F, Chen J Aging (Albany NY). 2024; 16(9):8031-8043.

PMID: 38713159 PMC: 11131980. DOI: 10.18632/aging.205803.

The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.

Sami Alkafaas S, Elsalahaty M, Ismail D, Ali Radwan M, Samy ElKafas S, Loutfy S Cancer Cell Int. 2024; 24(1):89.

PMID: 38419070 PMC: 10903003. DOI: 10.1186/s12935-024-03221-8.

Ceramide-1-phosphate transfer protein enhances lipid transport by disrupting hydrophobic lipid-membrane contacts.

Rogers J, Geissler P PLoS Comput Biol. 2023; 19(4):e1010992.

PMID: 37036851 PMC: 10085062. DOI: 10.1371/journal.pcbi.1010992.

References

Raya A, Revert F, Navarro S, Saus J . Characterization of a novel type of serine/threonine kinase that specifically phosphorylates the human goodpasture antigen. J Biol Chem. 1999; 274(18):12642-9. DOI: 10.1074/jbc.274.18.12642. View

Yasuda S, Kitagawa H, Ueno M, Ishitani H, Fukasawa M, Nishijima M . A novel inhibitor of ceramide trafficking from the endoplasmic reticulum to the site of sphingomyelin synthesis. J Biol Chem. 2001; 276(47):43994-4002. DOI: 10.1074/jbc.M104884200. View

Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M . Molecular machinery for non-vesicular trafficking of ceramide. Nature. 2003; 426(6968):803-9. DOI: 10.1038/nature02188. View

Fullekrug J, Simons K . Lipid rafts and apical membrane traffic. Ann N Y Acad Sci. 2004; 1014:164-9. DOI: 10.1196/annals.1294.017. View

Malinina L, Malakhova M, Teplov A, Brown R, Patel D . Structural basis for glycosphingolipid transfer specificity. Nature. 2004; 430(7003):1048-53. PMC: 2640488. DOI: 10.1038/nature02856. View

Golub T, Wacha S, Caroni P . Spatial and temporal control of signaling through lipid rafts. Curr Opin Neurobiol. 2004; 14(5):542-50. DOI: 10.1016/j.conb.2004.08.003. View

Rao C, Lin X, Pike H, Molotkovsky J, Brown R . Glycolipid transfer protein mediated transfer of glycosphingolipids between membranes: a model for action based on kinetic and thermodynamic analyses. Biochemistry. 2004; 43(43):13805-15. PMC: 2596630. DOI: 10.1021/bi0492197. View

Holthuis J, Levine T . Lipid traffic: floppy drives and a superhighway. Nat Rev Mol Cell Biol. 2005; 6(3):209-20. DOI: 10.1038/nrm1591. View

Rao C, Chung T, Pike H, Brown R . Glycolipid transfer protein interaction with bilayer vesicles: modulation by changing lipid composition. Biophys J. 2005; 89(6):4017-28. PMC: 1366967. DOI: 10.1529/biophysj.105.070631. View

10.

Airenne T, Kidron H, Nymalm Y, Nylund M, West G, Mattjus P . Structural evidence for adaptive ligand binding of glycolipid transfer protein. J Mol Biol. 2005; 355(2):224-36. DOI: 10.1016/j.jmb.2005.10.031. View

11.

van Meer G, Halter D, Sprong H, Somerharju P, Egmond M . ABC lipid transporters: extruders, flippases, or flopless activators?. FEBS Lett. 2005; 580(4):1171-7. DOI: 10.1016/j.febslet.2005.12.019. View

12.

Kawano M, Kumagai K, Nishijima M, Hanada K . Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT. J Biol Chem. 2006; 281(40):30279-88. DOI: 10.1074/jbc.M605032200. View

13.

Brown R, Mattjus P . Glycolipid transfer proteins. Biochim Biophys Acta. 2007; 1771(6):746-60. PMC: 1986823. DOI: 10.1016/j.bbalip.2007.01.011. View

14.

Lahiri S, Futerman A . The metabolism and function of sphingolipids and glycosphingolipids. Cell Mol Life Sci. 2007; 64(17):2270-84. PMC: 11136246. DOI: 10.1007/s00018-007-7076-0. View

15.

Swanton C, Marani M, Pardo O, Warne P, Kelly G, Sahai E . Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. Cancer Cell. 2007; 11(6):498-512. DOI: 10.1016/j.ccr.2007.04.011. View

16.

DAngelo G, Polishchuk E, Di Tullio G, Santoro M, Di Campli A, Godi A . Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide. Nature. 2007; 449(7158):62-7. DOI: 10.1038/nature06097. View

17.

Halter D, Neumann S, van Dijk S, Wolthoorn J, De Maziere A, Vieira O . Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis. J Cell Biol. 2007; 179(1):101-15. PMC: 2064740. DOI: 10.1083/jcb.200704091. View

18.

Saito S, Matsui H, Kawano M, Kumagai K, Tomishige N, Hanada K . Protein phosphatase 2Cepsilon is an endoplasmic reticulum integral membrane protein that dephosphorylates the ceramide transport protein CERT to enhance its association with organelle membranes. J Biol Chem. 2008; 283(10):6584-93. DOI: 10.1074/jbc.M707691200. View

19.

Hannun Y, Obeid L . Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol. 2008; 9(2):139-50. DOI: 10.1038/nrm2329. View

20.

West G, Viitanen L, Alm C, Mattjus P, Salminen T, Edqvist J . Identification of a glycosphingolipid transfer protein GLTP1 in Arabidopsis thaliana. FEBS J. 2008; 275(13):3421-37. DOI: 10.1111/j.1742-4658.2008.06498.x. View