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Cancer and Metastasis Reviews

, Volume 37, Issue 2–3, pp 245–255 | Cite as

The role of lipid signaling in the progression of malignant melanoma

  • József TímárEmail author
  • B. Hegedüs
  • E. Rásó
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.

Keywords

Eicosanoid Signaling Melanoma Cyclooxygenase Lipoxygenase Phosphodiestherase-2 

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

Notes

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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.2nd Department of PathologySemmelweis UniversityBudapestHungary
  2. 2.Molecular Oncology Research GroupSemmelweis UniversityBudapestHungary
  3. 3.Department of Throracic SurgeryUniversity Hospital EssenEssenGermany

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