Year: 2023
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: U.S. Department of Health and Human Services, American Cancer Society, Melanoma Research Alliance, Memorial Sloan-Kettering Cancer Center, Pershing Square Sohn Cancer Research Alliance, Mark Foundation For Cancer Research, Debra and Leon Black Family Foundation, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: Evolutionary dynamics of melanoma metastasis, G1605274011, G1676388581, G1808003726, G2051006376, G2238022421, Investigating the role of fatty acid metabolism in melanocyte differentiation: Insights into the metabolic requirements of development, G2665966410, G2695487608, G289723095, G3046438608, G3945460756, G4102770861, G4184184117, G4266131079, G4663426322, G5071749142, G5673257561, Investigating cancer metabolism and its potential for therapeutic intervention, G6403603385, G6680673728, In vivo characterization of keratinocytes in the melanoma microenvironment, G736417445, Dissecting the complexity of metastasis with mathematical models and quantitative experiments with in zebrafish, G8099233186, G8322667947, G8917572031, G9000003249, G9000007006, G9000034144, G9000084110, G9000126742, G9000206085, G9000224218, G9000303076, Cancer Center Support Grant
OpenAlex ID: W4379197226