Lipid droplets are a metabolic vulnerability in melanoma.
Lipid droplets are a metabolic vulnerability in melanoma.
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DOI：
10.1038/s41467-023-38831-9
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发表时间：
2023-06-02
影响因子：
16.6
通讯作者：
White, Richard M. M.
中科院分区：
文献类型：
--
作者：
Lumaquin-Yin, Dianne;Montal, Emily;Johns, Eleanor;Baggiolini, Arianna;Huang, Ting-Hsiang;Ma, Yilun;LaPlante, Charlotte;Suresh, Shruthy;Studer, Lorenz;White, Richard M. M.
黑色素瘤表现出多种转录细胞状态，包括神经嵴样细胞以及色素黑素细胞。这些不同的细胞状态如何与不同的致瘤表型相关仍不清楚。在这里，我们使用斑马鱼黑色素瘤模型来识别将黑素细胞状态与脂滴依赖性联系起来的转录程序，脂滴是负责脂质储存的特殊细胞器。这些肿瘤的单细胞 RNA 测序显示调节色素沉着的基因与参与脂质和氧化代谢的基因之间存在一致性。这种状态在人类黑色素瘤细胞系和患者肿瘤中是保守的。这种黑素细胞状态表明脂肪酸摄取增加、脂滴数量增加以及对脂肪酸氧化代谢的依赖性。脂滴产生的遗传和药理学抑制足以破坏细胞周期进程并减缓体内黑色素瘤的生长。由于黑素细胞状态与患者的不良预后有关，这些数据表明黑色素瘤的代谢脆弱性取决于脂滴细胞器。脂滴是一种动态细胞器，存在于多种细胞类型中，最常见的是脂肪细胞。在这里，作者在斑马鱼和人类细胞中发现，脂滴富含于促进癌症形成和生长的黑色素瘤细胞亚群中。
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. Lipid droplets are a dynamic organelle found in a variety of cell types, most prominently in adipocytes. Here, the authors find in zebrafish and human cells that lipid droplets are enriched in a subset of melanoma cells that promote cancer formation and growth.
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影响因子：
4.3
作者：
Callahan SJ;Tepan S;Zhang YM;Lindsay H;Burger A;Campbell NR;Kim IS;Hollmann TJ;Studer L;Mosimann C;White RM
通讯作者：
White RM
影响因子：
29
作者：
Cheng, Xiang;Geng, Feng;Guo, Deliang
通讯作者：
Guo, Deliang
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
--
作者：
Dubikovskaya, Elena;Chudnovskiy, Rostislav;Karateev, Grigory;Park, Hyo Min;Stahl, Andreas
通讯作者：
Stahl, Andreas
影响因子：
9.3
作者：
Baron M;Tagore M;Hunter MV;Kim IS;Moncada R;Yan Y;Campbell NR;White RM;Yanai I
通讯作者：
Yanai I