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

IF 3.9 3区医学 Q2 CELL BIOLOGY Pigment Cell & Melanoma Research Pub Date : 2024-10-31 DOI:10.1111/pcmr.13208

Eleanor Johns, Yilun Ma, Pakavarin Louphrasitthiphol, Christopher Peralta, Miranda V Hunter, Jeremy H Raymond, Henrik Molina, Colin R Goding, Richard M White

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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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脂滴蛋白 DHRS3 是黑色素瘤细胞状态的调控因子

脂滴是一种脂肪储存细胞器，由蛋白质包膜和富含脂质的核心组成。对这种蛋白质包膜的调节是脂滴形成和功能差异的基础。在黑色素瘤中，脂滴的形成与肿瘤的进展和转移有关，但脂滴蛋白是否在其中发挥作用尚不清楚。为了解决这个问题，我们对黑色素瘤的脂滴包膜进行了蛋白质组学分析。我们发现，脂滴蛋白在不同的黑色素瘤状态（从黑色素细胞瘤到未分化瘤）中富集程度不同。DHRS3能将全反式视黄醛转化为全反式视黄醇，它在MITFLO/未分化/神经嵴样黑色素瘤细胞状态中上调，而在MITFHI/黑色素细胞状态中降低。DHRS3 表达的增加足以使 MITFHI/黑素细胞细胞进入未分化/侵袭状态。这些变化是由于视黄酸介导的黑色素细胞基因调控所致。我们的数据表明，黑色素瘤细胞的状态可以通过脂滴蛋白的表达来调节，而脂滴蛋白的表达会影响下游的视黄酸信号转导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pigment Cell & Melanoma Research 医学-皮肤病学

CiteScore

8.90

自引率

2.30%

发文量

审稿时长

6-12 weeks

期刊介绍： Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders