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Cited by 9Lipid metabolism and biosynthesisCancer, Lipids, and MetabolismMelanoma and MAPK Pathways

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The Lipid Droplet Protein DHRS3 Is a Regulator of Melanoma Cell State

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Johns, Eleanor, Ma, Yilun, Louphrasitthiphol, Pakavarin, Peralta, Christopher, Hunter, Miranda V., Raymond, Jeremy H., Molina, Henrik, Goding, Colin R., White, Richard M.·2025·Pigment Cell & Melanoma Research
DOI 10.1111/pcmr.13208PMC PMC12244328

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Abstract

Lipid droplets are fat storage organelles composed of a protein envelope and lipid‐rich core. Regulation of this protein envelope underlies differential lipid droplet formation and function. In melanoma, lipid droplet formation has been linked to tumor progression and metastasis, but it is unknown whether lipid droplet proteins play a role. To address this, we performed proteomic analysis of the lipid droplet envelope in melanoma. We found that lipid droplet proteins were differentially enriched in distinct melanoma states; from melanocytic to undifferentiated. DHRS3, which converts all‐trans‐retinal to all‐trans‐retinol, is upregulated in the MITF LO /undifferentiated/neural crest‐like melanoma cell state and reduced in the MITF HI /melanocytic state. Increased DHRS3 expression is sufficient to drive MITF HI /melanocytic cells to a more undifferentiated/invasive state. These changes are due to retinoic acid‐mediated regulation of melanocytic genes. Our data demonstrate that melanoma cell state can be regulated by expression of lipid droplet proteins which affect downstream retinoid signaling.

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Metadata

Authors
Johns, E., Ma, Y., Louphrasitthiphol, P., Peralta, C., Hunter, M. V., Raymond, J. H., Molina, H., Goding, C. R., & White, R. M.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • University of Oxford (GB)
  • Rockefeller University (US)
  • Ludwig Institute for Cancer Research University of Oxford Oxford UK
Corresponding author
White, Richard M.
ORCID
Venue
Pigment Cell & Melanoma Research
Publisher
Wiley
Published
2024-10-31
Volume
38
Issue
1
Pages
e13208-e13208
ISSN
  • 1755-1471 (ISSN-L)
  • 1755-148X
DOI
10.1111/pcmr.13208
PMC
PMC12244328
OpenAlex
W4403954013
Cited by
9
References
7
Citations by year
2026: 4 · 2025: 5
FWCI
1.44
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Pigment Cell & Melanoma Research (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Institutes of Health (R01 CA268597‐01, T32GM007739, P30 CA008748, R01CA229215, R01CA238317)
  • National Cancer Institute (K99CA266931)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (F31AR079215)
  • Mark Foundation For Cancer Research
  • Pershing Square Foundation
  • Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center
  • American Cancer Society
  • Harry J. Lloyd Charitable Trust
  • Melanoma Research Alliance
  • Ludwig Institute for Cancer Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords
DHRS3, lipid droplets, melanoma, MITF, retinoid signaling, retinoic acid, all-trans-retinol, melanocyte differentiation, tumor invasion, neural crest-like cells, proteomics

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