Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage.

Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage.
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DOI:
10.3390/biomedicines10081943
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发表时间:
2022-08-11
期刊:
影响因子:
4.7
通讯作者:
--
中科院分区:
工程技术3区
文献类型:
--
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胶质母细胞瘤(GBM)是最致命的原发性脑肿瘤。由于治疗选择有限,迫切需要新的治疗方法。最近的研究表明,GBM通过激活固醇调节元件结合蛋白1(SREBP-1)(一种调节脂肪酸和胆固醇合成以及胆固醇摄取的主转录因子)获得大量脂质以快速生长。有趣的是,GBM细胞将大量的脂质转移到脂滴(LD)中,脂滴是中性脂质的特定储存细胞器,通过增加二酰基甘油酰基转移酶1(DGAT 1)和甾醇-O-酰基转移酶1(SOAT 1)的表达来防止脂毒性,DGAT 1和SOAT 1分别将过量的脂肪酸和胆固醇转化为三酰基甘油和胆固醇酯。在这篇综述中,我们将总结最近的进展,我们了解GBM的脂质代谢调节,以促进肿瘤生长,并讨论新的策略,特别是诱导脂毒性肿瘤细胞通过破坏脂质储存,一个有前途的新途径治疗GBM。
Glioblastoma (GBM) is the most lethal primary brain tumor. With limited therapeutic options, novel therapies are desperately needed. Recent studies have shown that GBM acquires large amounts of lipids for rapid growth through activation of sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor that regulates fatty acid and cholesterol synthesis, and cholesterol uptake. Interestingly, GBM cells divert substantial quantities of lipids into lipid droplets (LDs), a specific storage organelle for neutral lipids, to prevent lipotoxicity by increasing the expression of diacylglycerol acyltransferase 1 (DGAT1) and sterol-O-acyltransferase 1 (SOAT1), which convert excess fatty acids and cholesterol to triacylglycerol and cholesteryl esters, respectively. In this review, we will summarize recent progress on our understanding of lipid metabolism regulation in GBM to promote tumor growth and discuss novel strategies to specifically induce lipotoxicity to tumor cells through disrupting lipid storage, a promising new avenue for treating GBM.
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