Lipid droplets are a metabolic vulnerability in melanoma Journal Article
| Authors: | Lumaquin-Yin, D.; Montal, E.; Johns, E.; Baggiolini, A.; Huang, T. H.; Ma, Y.; LaPlante, C.; Suresh, S.; Studer, L.; White, R. M. |
| Article Title: | Lipid droplets are a metabolic vulnerability in melanoma |
| 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. © 2023, The Author(s). |
| Keywords: | genetics; animal; metabolism; animals; melanoma; melanocyte; melanocytes; pathology; fatty acids; fatty acid; lipid metabolism; zebra fish; zebrafish; fat droplet; lipid droplets; humans; human |
| Journal Title: | Nature Communications |
| Volume: | 14 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-06-02 |
| Start Page: | 3192 |
| Language: | English |
| DOI: | 10.1038/s41467-023-38831-9 |
| PUBMED: | 37268606 |
| PROVIDER: | scopus |
| PMCID: | PMC10238408 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Richard White -- Source: Scopus |
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