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| Status |
Public on Mar 26, 2023 |
| Title |
Lipid droplets are a metabolic vulnerability in melanoma |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| |
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| Overall design |
Expression profiling by high throughput sequencing of zebrafish melanoma
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| |
|
| Contributor(s) |
Lumaquin-Yin D, White RM |
| Citation(s) |
37268606 |
| Submission date |
Apr 23, 2022 |
| Last update date |
Jun 25, 2023 |
| Contact name |
Dianne Lumaquin |
| E-mail(s) |
dil2009@med.cornell.edu
|
| Organization name |
Memorial Sloan Kettering Cancer Center
|
| Department |
Cancer Biology and Genetics
|
| Lab |
Richard M. White
|
| Street address |
417 E 68th ST
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24995 |
Illumina NovaSeq 6000 (Danio rerio) |
|
| Samples (7)
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| Relations |
| BioProject |
PRJNA831276 |
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