Sphingolipids and Lymphomas: A Double-Edged Sword

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 May 14

PMID 35565181

Authors

Alfredo Pherez-Farah

Rosa Del Carmen Lopez-Sanchez

Luis Mario Villela-Martinez

Rocio Ortiz-Lopez

Brady E Beltran

Jose Ascencion Hernandez-Hernandez

Affiliations

Soon will be listed here.

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.

Citing Articles

The Role of Sphingolipid Metabolism in Pregnancy-Associated Breast Cancer After Chemotherapy.

Blokhin V, Zavarykina T, Kotsuba V, Kapralova M, Gutner U, Shupik M Biomedicines. 2025; 12(12.

PMID: 39767749 PMC: 11673991. DOI: 10.3390/biomedicines12122843.

The role of ceranib-2 and its nanoform on the decrease of telomerase levels in human non-small cell cancer.

Cengiz M, Sezer C, Gur B, Bayrakdar A, Izgordu H, Alanyali F Mol Biol Rep. 2024; 51(1):889.

PMID: 39105852 DOI: 10.1007/s11033-024-09838-2.

Leveraging altered lipid metabolism in treating B cell malignancies.

Lee J, Mani A, Shin M, Krauss R Prog Lipid Res. 2024; 95:101288.

PMID: 38964473 PMC: 11347096. DOI: 10.1016/j.plipres.2024.101288.

Metabolic Biomarkers Affecting Cell Proliferation and Prognosis in Polycythemia Vera.

Wang Z, Lv Y, Yang E, Li Y, Wang D, Hu G Cancers (Basel). 2022; 14(19).

PMID: 36230834 PMC: 9563618. DOI: 10.3390/cancers14194913.

References

Ghandour B, Pisano C, Darwiche N, Dbaibo G . Restoration of ceramide de novo synthesis by the synthetic retinoid ST1926 as it induces adult T-cell leukemia cell death. Biosci Rep. 2020; 40(10). PMC: 7593536. DOI: 10.1042/BSR20200050. View

Alonso-Alonso R, Mondejar R, Martinez N, Garcia-Diaz N, Perez C, Merino D . Identification of tipifarnib sensitivity biomarkers in T-cell acute lymphoblastic leukemia and T-cell lymphoma. Sci Rep. 2020; 10(1):6721. PMC: 7174413. DOI: 10.1038/s41598-020-63434-5. View

Fan Q, Cheng Y, Chang H, Deguchi M, Hsueh A, Leung P . Sphingosine-1-phosphate promotes ovarian cancer cell proliferation by disrupting Hippo signaling. Oncotarget. 2017; 8(16):27166-27176. PMC: 5432326. DOI: 10.18632/oncotarget.15677. View

Venkatanarayanan S, Nagarajan B . Multiple marker validity of urinary hexosaminidase and polyamines in haematopoietic malignancy. Biochem Int. 1989; 18(2):301-9. View

Qiu Y, Yun M, Dong X, Xu M, Zhao R, Han X . Combination of cytokine-induced killer and dendritic cells pulsed with antigenic α-1,3-galactosyl epitope-enhanced lymphoma cell membrane for effective B-cell lymphoma immunotherapy. Cytotherapy. 2015; 18(1):91-8. DOI: 10.1016/j.jcyt.2015.09.012. View

Hasan I, Sugawara S, Fujii Y, Koide Y, Terada D, Iimura N . MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt's Lymphoma Cells to Trigger Apoptosis through Multiple Pathways. Mar Drugs. 2015; 13(12):7377-89. PMC: 4699244. DOI: 10.3390/md13127071. View

Singh R, Shaik S, Negi B, Rajguru J, Patil P, Parihar A . Non-Hodgkin's lymphoma: A review. J Family Med Prim Care. 2020; 9(4):1834-1840. PMC: 7346945. DOI: 10.4103/jfmpc.jfmpc_1037_19. View

Jarvis R, Chamba A, Holder M, Challa A, Smith D, Hodgkin M . Dynamic interplay between the neutral glycosphingolipid CD77/Gb3 and the therapeutic antibody target CD20 within the lipid bilayer of model B lymphoma cells. Biochem Biophys Res Commun. 2007; 355(4):944-9. DOI: 10.1016/j.bbrc.2007.02.053. View

van der Luit A, Vink S, Klarenbeek J, Perrissoud D, Solary E, Verheij M . A new class of anticancer alkylphospholipids uses lipid rafts as membrane gateways to induce apoptosis in lymphoma cells. Mol Cancer Ther. 2007; 6(8):2337-45. DOI: 10.1158/1535-7163.MCT-07-0202. View

10.

Choi H, Chung T, Kang S, Lee Y, Ko J, Kim J . Ganglioside GM3 modulates tumor suppressor PTEN-mediated cell cycle progression--transcriptional induction of p21(WAF1) and p27(kip1) by inhibition of PI-3K/AKT pathway. Glycobiology. 2006; 16(7):573-83. DOI: 10.1093/glycob/cwj105. View

11.

Makena M, Nguyen T, Koneru B, Hindle A, Chen W, Verlekar D . Vorinostat and fenretinide synergize in preclinical models of T-cell lymphoid malignancies. Anticancer Drugs. 2020; 32(1):34-43. DOI: 10.1097/CAD.0000000000001008. View

12.

van der Hoeven D, Cho K, Zhou Y, Ma X, Chen W, Naji A . Sphingomyelin Metabolism Is a Regulator of K-Ras Function. Mol Cell Biol. 2017; 38(3). PMC: 5770534. DOI: 10.1128/MCB.00373-17. View

13.

Steelant W, Kawakami Y, Ito A, Handa K, Bruyneel E, Mareel M . Monosialyl-Gb5 organized with cSrc and FAK in GEM of human breast carcinoma MCF-7 cells defines their invasive properties. FEBS Lett. 2002; 531(1):93-8. DOI: 10.1016/s0014-5793(02)03484-1. View

14.

Baeyens A, Schwab S . Finding a Way Out: S1P Signaling and Immune Cell Migration. Annu Rev Immunol. 2020; 38:759-784. DOI: 10.1146/annurev-immunol-081519-083952. View

15.

Liu Y, Patwardhan G, Bhinge K, Gupta V, Gu X, Jazwinski S . Suppression of glucosylceramide synthase restores p53-dependent apoptosis in mutant p53 cancer cells. Cancer Res. 2011; 71(6):2276-85. PMC: 3059346. DOI: 10.1158/0008-5472.CAN-10-3107. View

16.

Govindarajah N, Clifford R, Bowden D, Sutton P, Parsons J, Vimalachandran D . Sphingolipids and acid ceramidase as therapeutic targets in cancer therapy. Crit Rev Oncol Hematol. 2019; 138:104-111. DOI: 10.1016/j.critrevonc.2019.03.018. View

17.

Jennemann R, Volz M, Bestvater F, Schmidt C, Richter K, Kaden S . Blockade of Glycosphingolipid Synthesis Inhibits Cell Cycle and Spheroid Growth of Colon Cancer Cells In Vitro and Experimental Colon Cancer Incidence In Vivo. Int J Mol Sci. 2021; 22(19). PMC: 8508865. DOI: 10.3390/ijms221910539. View

18.

Huang Y, Wu S, Zhang Y, Zi Y, Yang M, Guo Y . [Ceramide participates in cell programmed death induced by Type II anti-CD20 mAb]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2016; 40(12):1292-7. DOI: 10.11817/j.issn.1672-7347.2015.12.002. View

19.

Modrak D, Cardillo T, Newsome G, Goldenberg D, Gold D . Synergistic interaction between sphingomyelin and gemcitabine potentiates ceramide-mediated apoptosis in pancreatic cancer. Cancer Res. 2004; 64(22):8405-10. DOI: 10.1158/0008-5472.CAN-04-2988. View

20.

Robert A, Wiels J . Shiga Toxins as Antitumor Tools. Toxins (Basel). 2021; 13(10). PMC: 8538568. DOI: 10.3390/toxins13100690. View