AUTHOR=Falletta Paola , Goding Colin R. , Vivas-García Yurena 

TITLE=Connecting Metabolic Rewiring With Phenotype Switching in Melanoma

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.930250

DOI=10.3389/fcell.2022.930250

ISSN=2296-634X

ABSTRACT=Melanoma is a complex and aggressive cancer type that contains different cell subpopulations displaying distinct phenotypes within the same tumour. Metabolic reprogramming, a hallmark of cell transformation, is essential for melanoma cells to adopt different phenotypic states necessary for adaptation to changes arising from a dynamic milieu and oncogenic background. Increasing evidence demonstrates how melanoma cells can exhibit distinct metabolic profiles depending on their specific phenotype, allowing adaptation to hostile microenvironmental conditions, such as hypoxia or nutrient depletion. For instance, increased glucose consumption and lipid anabolism are associated with proliferation, while a dependency on exogenous fatty acids and an oxidative state are linked to invasion and metastatic dissemination. How these different metabolic dependencies are integrated with specific cell phenotypes is poorly understood and little is known about metabolic changes underpinning melanoma metastasis. Recent evidence suggests that metabolic rewiring engaging transitions to invasion and metastatic progression may be dependent on several factors, such as specific oncogenic programs or lineage-restricted mechanisms controlling cell metabolism, intra-tumour microenvironmental cues and also site-specificity of metastasis. In this review we will highlight how the main molecular events supporting melanoma metabolic rewiring and phenotype-switching are parallel and interconnected events that through interplay with the tumour microenvironment dictate tumour progression and metastatic dissemination.