PUBLICATION
Lipid droplets are a metabolic vulnerability in melanoma
- Authors
- Lumaquin-Yin, D., Montal, E., Johns, E., Baggiolini, A., Huang, T.H., Ma, Y., LaPlante, C., Suresh, S., Studer, L., White, R.M.
- ID
- ZDB-PUB-230604-35
- Date
- 2023
- Source
- Nature communications 14: 31923192 (Journal)
- Registered Authors
- White, Richard M.
- Keywords
- none
- Datasets
- GEO:GSE201378
- MeSH Terms
-
- Animals
- Fatty Acids/metabolism
- Humans
- Lipid Droplets*/metabolism
- Lipid Metabolism/genetics
- Melanocytes/metabolism
- Melanoma*/pathology
- Zebrafish/genetics
- PubMed
- 37268606 Full text @ Nat. Commun.
Citation
Lumaquin-Yin, D., Montal, E., Johns, E., Baggiolini, A., Huang, T.H., Ma, Y., LaPlante, C., Suresh, S., Studer, L., White, R.M. (2023) Lipid droplets are a metabolic vulnerability in melanoma. Nature communications. 14:31923192.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping