LB996 Lipid droplets are a metabolic vulnerability in melanoma

Melanoma cells exhibit numerous transcriptional cell states including developmental programs such as neural crest-like and pigmented melanocytic cells. These endow tumorigenic properties like sustained growth, immune evasion, therapy resistance, metastasis. Here, we use a zebrafish melanoma model to identify program linking the state dependence on lipid droplets, specialized organelle responsible for storage. Single-cell RNA-sequencing of these tumors show concordance between genes regulating pigmentation those involved in oxidative metabolism. This metabolic phenotype is conserved human specimens. demonstrates increased fatty acid uptake, an number upon Genetic pharmacologic suppression droplet production sufficient disrupt metabolism slow growth vivo. Because linked poor outcomes patients, data indicate vulnerability that depends organelle.