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Review
. 2020 Aug 26;9(9):1967.
doi: 10.3390/cells9091967.

New Insights into the Role of Sphingolipid Metabolism in Melanoma

Lorry Carrié  1 , Mathieu Virazels  1 , Carine Dufau  1 , Anne Montfort  1 , Thierry Levade  1   2 , Bruno Ségui  1 , Nathalie Andrieu-Abadie  1
Affiliations
Review

New Insights into the Role of Sphingolipid Metabolism in Melanoma

Lorry Carrié et al. Cells. .

Abstract

Cutaneous melanoma is a deadly skin cancer whose aggressiveness is directly linked to its metastatic potency. Despite remarkable breakthroughs in term of treatments with the emergence of targeted therapy and immunotherapy, the prognosis for metastatic patients remains uncertain mainly because of resistances. Better understanding the mechanisms responsible for melanoma progression is therefore essential to uncover new therapeutic targets. Interestingly, the sphingolipid metabolism is dysregulated in melanoma and is associated with melanoma progression and resistance to treatment. This review summarises the impact of the sphingolipid metabolism on melanoma from the initiation to metastatic dissemination with emphasis on melanoma plasticity, immune responses and resistance to treatments.

Keywords: cancer; ceramide; gangliosides; immunotherapy; metastasis; phenotype switching; sphingosine 1-phosphate.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cutaneous melanoma: the 19th most common cancer worldwide. Estimated age-standardised incidence rates of cutaneous melanoma in the most affected countries in 2018, for both sexes and all ages. Data from the International Agency for Research on Cancer (World Health Organisation).
Figure 2
Figure 2
BRAF, NRAS, PTEN and CDKN2A are the most frequently mutated genes in cutaneous melanoma. Mutation rate, genetic alteration (a) and mutual exclusivity (b) for BRAF, NRAS, PTEN and CDKN2A mutations observed in 1635 samples from 1584 patients included in 12 studies analysed on cBioportal for cancer genomics (https://www.cbioportal.org).
Figure 3
Figure 3
Multiple dysregulations of sphingolipid metabolism in melanoma. SL metabolites or SL-metabolising enzymes whose levels or expression are altered in melanoma, are mentioned. Decreases are indicated in blue and increases in red. AC, acid ceramidase; Cer, ceramide; CERS, ceramide synthase; CoA, coenzyme A; DihydroCer, dihydroceramide; GalCer, galactosylceramide; GC, glucosylceramidase; GlcCer, glucosylceramide; LacCer, lactosylceramide; S, sphingosine; S1P, sphingosine 1-phosphate; SM, sphingomyelin; SMases, sphingomyelinases; SMS, sphingomyelin synthase; SPC, sphingosylphosphorylcholine; SphK, sphingosine kinase; SPL, S1P lyase; ULCFA, ultralong chain fatty acids.
Figure 4
Figure 4
Role of sphingolipid metabolism in melanoma progression and immune response. SL metabolites and SL-metabolising enzymes whose levels and expression are increased, decreased or implicated are marked in red, blue or black, respectively. AC, acid ceramidase; CD8+, CD8+ T cells; Cer, ceramide; CerS, ceramide synthase; GC, glucosylceramidase; GCS, glucosylceramide synthase; M1, M1 macrophages; M2, M2 macrophages; MDSC, myeloid-derived suppressor cells; NK, natural killer cells; NKT, natural killer T cells; S1P, sphingosine 1-phosphate; S1P1/2/3, S1P receptor type 1/2/3; SMases, sphingomyelinases; SMS, sphingomyelin synthase; SPC, sphingosylphosphorylcholine; SphK, sphingosine kinase; SPL, S1P lyase; Th1, Th1 CD4+ T cells; Treg, tegulatory T cells.
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References

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