Inhibition of Fatty Acid Synthase Decreases Expression of Stemness Markers in Glioma Stem Cells.
Inhibition of Fatty Acid Synthase Decreases Expression of Stemness Markers in Glioma Stem Cells.
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脂肪酸合酶的抑制会降低神经胶质瘤干细胞中干性标记的表达。
DOI：
10.1371/journal.pone.0147717
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Owada Y
中科院分区：
文献类型：
--
作者：
Yasumoto Y;Miyazaki H;Vaidyan LK;Kagawa Y;Ebrahimi M;Yamamoto Y;Ogata M;Katsuyama Y;Sadahiro H;Suzuki M;Owada Y
细胞代谢变化，特别是脂质代谢的变化，最近被认为是各种癌细胞的标志。然而，关于细胞脂质代谢在胶质瘤干细胞（GSCs）生物学活性调节中的意义知之甚少。在这项研究中，我们研究了脂肪酸合成酶（FATCH），一种关键的脂肪生成酶，在GSC中的表达和作用。在从头脂质合成测定中，GSC表现出比分化的非GSC更高的脂肪生成。Western印迹和免疫细胞化学分析显示，FcB在多种来源于患者的GSC（G144和Y10）中强烈表达，但其表达在分化后显著降低。当用20 μM浅蓝菌素（一种Festival的药理学抑制剂）处理GSC时，它们的增殖和迁移受到显著抑制，新生脂肪生成减少。此外，浅蓝菌素治疗后，GSC标志物巢蛋白，Sox 2和脂肪酸结合蛋白（FABP7），GCSs的标志物，表达下降，而胶质细胞酸性蛋白（GFAP）的表达增加。总之，我们的研究结果表明，FASN在维持GSC干性中起着关键作用，FASN介导的从头脂质生物合成与胶质母细胞瘤的肿瘤生长和侵袭密切相关。
Cellular metabolic changes, especially to lipid metabolism, have recently been recognized as a hallmark of various cancer cells. However, little is known about the significance of cellular lipid metabolism in the regulation of biological activity of glioma stem cells (GSCs). In this study, we examined the expression and role of fatty acid synthase (FASN), a key lipogenic enzyme, in GSCs. In the de novo lipid synthesis assay, GSCs exhibited higher lipogenesis than differentiated non-GSCs. Western blot and immunocytochemical analyses revealed that FASN is strongly expressed in multiple lines of patient-derived GSCs (G144 and Y10), but its expression was markedly reduced upon differentiation. When GSCs were treated with 20 μM cerulenin, a pharmacological inhibitor of FASN, their proliferation and migration were significantly suppressed and de novo lipogenesis decreased. Furthermore, following cerulenin treatment, expression of the GSC markers nestin, Sox2 and fatty acid binding protein (FABP7), markers of GCSs, decreased while that of glial fibrillary acidic protein (GFAP) expression increased. Taken together, our results indicate that FASN plays a pivotal role in the maintenance of GSC stemness, and FASN-mediated de novo lipid biosynthesis is closely associated with tumor growth and invasion in glioblastoma.