Metabolic Plasticity of Melanoma Cells and Their Crosstalk With Tumor Microenvironment

Frontiers in Oncology
Angelica AvaglianoAlessandro Arcucci

Abstract

Cutaneous melanoma (CM) is a highly aggressive and drug resistant solid tumor, showing an impressive metabolic plasticity modulated by oncogenic activation. In particular, melanoma cells can generate adenosine triphosphate (ATP) during cancer progression by both cytosolic and mitochondrial compartments, although CM energetic request mostly relies on glycolysis. The upregulation of glycolysis is associated with constitutive activation of BRAF/MAPK signaling sustained by BRAFV600E kinase mutant. In this scenario, the growth and progression of CM are strongly affected by melanoma metabolic changes and interplay with tumor microenvironment (TME) that sustain tumor development and immune escape. Furthermore, CM metabolic plasticity can induce a metabolic adaptive response to BRAF/MEK inhibitors (BRAFi/MEKi), associated with the shift from glycolysis toward oxidative phosphorylation (OXPHOS). Therefore, in this review article we survey the metabolic alterations and plasticity of CM, its crosstalk with TME that regulates melanoma progression, drug resistance and immunosurveillance. Finally, we describe hallmarks of melanoma therapeutic strategies targeting the shift from glycolysis toward OXPHOS.

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Citations

Jun 19, 2020·International Journal of Molecular Sciences·Eleonora VecchioIleana Quinto
Nov 19, 2020·British Journal of Cancer·Prakrit R KumarMarc D Moncrieff
Jan 13, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Cheila BritoMarta Pojo
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Mar 18, 2021·European Biophysics Journal : EBJ·Anna SobiepanekTomasz Kobiela
Jun 3, 2021·International Journal of Molecular Sciences·Dorina CoricovacMirela Danina Muntean
Jun 3, 2021·Life·Jiri Vachtenheim, Lubica Ondrušová
Jun 3, 2021·International Journal of Molecular Sciences·Veronica RomanoAlessandro Arcucci
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Jul 22, 2021·Journal of Cellular and Molecular Medicine·Xian Rui WuJianda Zhou

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Methods Mentioned

BETA
xenografts
deamination
transgenic
protein folding
biopsies
xenograft

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