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The role of lipid signaling in the progression of malignant melanoma

Cancer and Metastasis Reviews volume 37, pages 245–255 (2018)Cite this article

Abstract

In the past decades, a vast amount of data accumulated on the role of lipid signaling pathways in the progression of malignant melanoma, the most metastatic/aggressive human cancer type. Genomic studies identified that PTEN loss is the leading factor behind the activation of the PI3K-signaling pathway in melanoma, mutations of which are one of the main resistance mechanisms behind target therapy failures. On the other hand, illegitimate expressions of megakaryocytic genes p12-lipoxyganse, cyclooxygenase-2, and phosphodiestherase-2/autotaxin (ATX) are mostly involved in the regulation of motility signaling in melanoma through various G-protein-coupled bioactive lipid receptors. Furthermore, endocannabinoid signaling can also be a novel paracrine survival factor in melanoma. Last but not least, prenylation inhibitors acting even on mutated small GTP-ases, such as NRAS of melanoma may offer novel therapeutic opportunities. As regards melanoma, the most effective therapy nowadays is immunotherapy, with the resistance mechanisms also possibly involving the lipid signaling activities of melanoma cells, which further supports the idea of their being therapeutic targets.

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Abbreviations

AA:

Arachidonic acid

AMF:

Autocrine motility factor

ATX:

Autotaxin

COX:

Cyclooxygenase

ENPP:

Ectonucleotide pyrophosphatase

FT:

Farnesyl transferase

GGT:

Geranylgeranyl transferase

GPCR:

G-protein-coupled receptor

HDAC:

Histone deacetylase

HETE:

Hydroxy tetraenoic acid

LOX:

Lypoxygenase

MMP:

Matrix metalloproteinase

NGS:

Next-generation sequencing

PG:

Prostaglandin

PI3K:

PI3 kinase

PL:

Phospholipase

PTGS:

Prostaglandin synthase

PUFA:

Poly-unsaturated fatty acid

p12-LOX:

Platelet-type 12-LOX

RTK:

Receptor tyrosine kinase

ZA:

Zoledronic acid

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Acknowledgements

This work was supported by the National R&D& Innovation Office, Hungary (NKFI-K-112371, NVKP-16-1-2016-0004 and -0020, NAPB/KTIA13-0021).

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Authors and Affiliations

  1. 2nd Department of Pathology, Semmelweis University, 93. Üllöi u, Budapest, 1091, Hungary

    József Tímár & E. Rásó

  2. Molecular Oncology Research Group, Semmelweis University, Budapest, Hungary

    József Tímár & B. Hegedüs

  3. Department of Throracic Surgery, University Hospital Essen, Essen, Germany

    B. Hegedüs

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  1. József Tímár
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  2. B. Hegedüs
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  3. E. Rásó
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Correspondence to József Tímár.

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Tímár, J., Hegedüs, B. & Rásó, E. The role of lipid signaling in the progression of malignant melanoma. Cancer Metastasis Rev 37, 245–255 (2018). https://doi.org/10.1007/s10555-018-9729-x

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Keywords

  • Eicosanoid
  • Signaling
  • Melanoma
  • Cyclooxygenase
  • Lipoxygenase
  • Phosphodiestherase-2