Paiardi Chiara, Mirzoyan Zhasmine, Zola Sheri, Parisi Federica, Vingiani Andrea, Pasini Maria Enrica, Bellosta Paola
Department of Biosciences, University of Milan, Via Celoria 26, 20133 Milan, Italy.
Center of Integrated Biology (CiBio), University of Trento, Via Sommarive 9, 38123 Trento, Italy.
Genes (Basel). 2017 Apr 28;8(5):131. doi: 10.3390/genes8050131.
Lipids are an important energy supply in our cells and can be stored or used to produce macromolecules during lipogenesis when cells experience nutrient starvation. Our proteomic analysis reveals that the homologue of human Stearoyl-CoA desaturase-1 Desat1) is an indirect target of Myc in fat cells. Stearoyl-CoA desaturases are key enzymes in the synthesis of monounsaturated fatty acids critical for the formation of complex lipids such as triglycerides and phospholipids. Their function is fundamental for cellular physiology, however in tumors, overexpression of SCD-1 and SCD-5 has been found frequently associated with a poor prognosis. Another gene that is often upregulated in tumors is the proto-oncogene , where its overexpression or increased protein stability, favor cellular growth. Here, we report a potential link between Myc and Desat1 to control autophagy and growth. Using , we found that expression of Desat1, in metabolic tissues like the fat body, in the gut and in epithelial cells, is necessary for Myc function to induce autophagy a cell eating mechanism important for energy production. In addition, we observed that reduction of Desat1 affects Myc ability to induce growth in epithelial cells. Our data also identify, in prostatic tumor cells, a significant correlation between the expression of Myc and SCD-1 proteins, suggesting the existence of a potential functional relationship between the activities of these proteins in sustaining tumor progression.
脂质是我们细胞中重要的能量来源，当细胞经历营养饥饿时，脂质可以被储存起来或用于在脂肪生成过程中产生大分子。我们的蛋白质组学分析表明，人类硬脂酰辅酶A去饱和酶-1（Desat1）的同源物是脂肪细胞中Myc的间接靶点。硬脂酰辅酶A去饱和酶是单不饱和脂肪酸合成中的关键酶，对甘油三酯和磷脂等复合脂质的形成至关重要。它们的功能对细胞生理至关重要，然而在肿瘤中，经常发现SCD-1和SCD-5的过表达与预后不良有关。另一个在肿瘤中经常上调的基因是原癌基因，其过表达或蛋白质稳定性增加有利于细胞生长。在这里，我们报告了Myc和Desat1之间潜在的联系，以控制自噬和生长。通过研究，我们发现在脂肪体、肠道和上皮细胞等代谢组织中，Desat1的表达对于Myc诱导自噬（一种对能量产生很重要的细胞吞噬机制）的功能是必要的。此外，我们观察到Desat1的减少会影响Myc在上皮细胞中诱导生长的能力。我们的数据还表明，在前列腺肿瘤细胞中，Myc和SCD-1蛋白的表达之间存在显著相关性，这表明这些蛋白的活性在维持肿瘤进展方面可能存在潜在的功能关系。
