The Lipid Droplet Protein <scp>DHRS3</scp> Is a Regulator of Melanoma Cell State
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<sup>LO</sup>/undifferentiated/neural crest-like melanoma cell state and reduced in the MITF<sup>HI</sup>/melanocytic state. Increased DHRS3 expression is sufficient to drive MITF<sup>HI</sup>/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.
Authors
- Colin R. Goding (ORCID: https://orcid.org/0000-0002-1614-3909)
- Miranda V. Hunter (ORCID: https://orcid.org/0000-0002-6971-1738)
- Henrik Molina (ORCID: https://orcid.org/0000-0001-8950-4990)
- Yilun Ma (ORCID: https://orcid.org/0000-0002-2297-9980)
- Pakavarin Louphrasitthiphol
- Richard M. White (ORCID: https://orcid.org/0000-0001-9099-9169)
- Eleanor Johns (ORCID: https://orcid.org/0000-0001-6802-041X)
- Christopher Peralta (ORCID: https://orcid.org/0009-0003-1801-3002)
- Jérémy H. Raymond (ORCID: https://orcid.org/0000-0002-8712-895X)
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- Cornell University (US)
- University of Oxford (GB)
- Tri-Institutional PhD Program in Chemical Biology (US)
- Ludwig Cancer Research (GB)
- Rockefeller University (US)
Publication Details
- Journal
- Pigment Cell & Melanoma Research
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1111/pcmr.13208
- Citations
- 7
- Primary Topic
- Lipid metabolism and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 2.06
Funders
- American Cancer Society
- Melanoma Research Alliance
- Harry J. Lloyd Charitable Trust
- Memorial Sloan-Kettering Cancer Center
- Ludwig Institute for Cancer Research
- Pershing Square Foundation
- Pershing Square Sohn Cancer Research Alliance
- Mark Foundation For Cancer Research
- Debra and Leon Black Family Foundation
- National Institutes of Health
- Weill Cornell Medical College
- Alan and Sandra Gerry Metastasis and Tumor Ecosystems Center
- National Cancer Institute
- National Institute of Arthritis and Musculoskeletal and Skin Diseases