The lipid droplet protein DHRS3 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 w...
| Main Authors: | , , , , , , , , |
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| Format: | Internet publication |
| Language: | English |
| Published: |
2024
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| _version_ | 1826313036105777152 |
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| author | Johns, E Ma, Y Louphrasitthipol, P Peralta, C Hunter, MV Raymond, JH Molina, H Goding, CR White, RM |
| author_facet | Johns, E Ma, Y Louphrasitthipol, P Peralta, C Hunter, MV Raymond, JH Molina, H Goding, CR White, RM |
| author_sort | Johns, E |
| collection | OXFORD |
| description | 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 MITFLO/undifferentiated/neural crest-like melanoma cell state and reduced in the MITFHI/melanocytic state. Increased DHRS3 expression is sufficient to drive MITFHI/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. |
| first_indexed | 2024-09-25T04:06:24Z |
| format | Internet publication |
| id | oxford-uuid:15841a38-30e3-4fc9-a3d6-ddb98821e25c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:06:24Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | oxford-uuid:15841a38-30e3-4fc9-a3d6-ddb98821e25c2024-06-03T10:56:47ZThe lipid droplet protein DHRS3 is a regulator of melanoma cell stateInternet publicationhttp://purl.org/coar/resource_type/c_7ad9uuid:15841a38-30e3-4fc9-a3d6-ddb98821e25cEnglishSymplectic Elements2024Johns, EMa, YLouphrasitthipol, PPeralta, CHunter, MVRaymond, JHMolina, HGoding, CRWhite, RMLipid 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 MITFLO/undifferentiated/neural crest-like melanoma cell state and reduced in the MITFHI/melanocytic state. Increased DHRS3 expression is sufficient to drive MITFHI/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. |
| spellingShingle | Johns, E Ma, Y Louphrasitthipol, P Peralta, C Hunter, MV Raymond, JH Molina, H Goding, CR White, RM The lipid droplet protein DHRS3 is a regulator of melanoma cell state |
| title | The lipid droplet protein DHRS3 is a regulator of melanoma cell state |
| title_full | The lipid droplet protein DHRS3 is a regulator of melanoma cell state |
| title_fullStr | The lipid droplet protein DHRS3 is a regulator of melanoma cell state |
| title_full_unstemmed | The lipid droplet protein DHRS3 is a regulator of melanoma cell state |
| title_short | The lipid droplet protein DHRS3 is a regulator of melanoma cell state |
| title_sort | lipid droplet protein dhrs3 is a regulator of melanoma cell state |
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