Melanoma/macrophage hybrids as models for melanoma metastasis

Rachkovsky, Michael; Sodi, Stefano; Chakraborty, Abhishek A.; AvissarY,; Bolognia, Jean L.; Madison, Jennifer; Bermudes, David; Pawelek, John M.

doi:10.1097/00008390-199706001-00189

Melanoma Research

1997

DOI: 10.1097/00008390-199706001-00189

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Melanoma/macrophage hybrids as models for melanoma metastasis

Michael Rachkovsky¹,

Stefano Sodi²,

Abhishek A. Chakraborty³

et al.

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2023

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“…In contrast, fewer studies have focused on the role of the pigmented, mature melanocytic cell state. Prior to terminal differentiation, these pigmented melanocytic cells remain highly proliferative, suggesting they may play a key role in tumor progression 9,14,15 . This state has translational importance since clinical data have correlated differentiated melanocytic identity with worse clinical outcomes [16][17][18][19] .…”

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Lipid droplets are a metabolic vulnerability in melanoma

et al. 2023

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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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confidence: 99%

Lipid droplets are a metabolic vulnerability in melanoma

et al. 2023

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Melanoma/macrophage hybrids as models for melanoma metastasis

Cited by 1 publication

References 0 publications

Lipid droplets are a metabolic vulnerability in melanoma

Lipid droplets are a metabolic vulnerability in melanoma

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