Lipid droplets are a metabolic vulnerability in melanoma

Dianne Lumaquin-Yin, Emily Montal, Eleanor Johns, Arianna Baggiolini, Ting-Hsiang Huang, Yilun Ma, Charlotte LaPlante, Shruthy Suresh, Lorenz Studer and Richard M. White ()
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Dianne Lumaquin-Yin: Memorial Sloan Kettering Cancer Center
Emily Montal: Memorial Sloan Kettering Cancer Center
Eleanor Johns: Memorial Sloan Kettering Cancer Center
Arianna Baggiolini: Memorial Sloan Kettering Cancer Center
Ting-Hsiang Huang: Memorial Sloan Kettering Cancer Center
Yilun Ma: Memorial Sloan Kettering Cancer Center
Charlotte LaPlante: Memorial Sloan Kettering Cancer Center
Shruthy Suresh: Memorial Sloan Kettering Cancer Center
Lorenz Studer: Memorial Sloan Kettering Cancer Center
Richard M. White: Memorial Sloan Kettering Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Melanoma exhibits numerous transcriptional cell states including neural crest-like cells as well as pigmented melanocytic cells. How these different cell states relate to distinct tumorigenic phenotypes remains unclear. Here, we use a zebrafish melanoma model to identify a transcriptional program linking the melanocytic cell state to a dependence on lipid droplets, the specialized organelle responsible for lipid storage. Single-cell RNA-sequencing of these tumors show a concordance between genes regulating pigmentation and those involved in lipid and oxidative metabolism. This state is conserved across human melanoma cell lines and patient tumors. This melanocytic state demonstrates increased fatty acid uptake, an increased number of lipid droplets, and dependence upon fatty acid oxidative metabolism. Genetic and pharmacologic suppression of lipid droplet production is sufficient to disrupt cell cycle progression and slow melanoma growth in vivo. Because the melanocytic cell state is linked to poor outcomes in patients, these data indicate a metabolic vulnerability in melanoma that depends on the lipid droplet organelle.

Date: 2023
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DOI: 10.1038/s41467-023-38831-9

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