Kou Yongjun, Geng Feng, Guo Deliang
Department of Radiation Oncology, Ohio State Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, College of Medicine at The Ohio State University, Columbus, OH 43012, USA.
Center for Cancer Metabolism, James Comprehensive Cancer Center at The Ohio State University, Columbus, OH 43210, USA.
Biomedicines. 2022 Aug 11;10(8):1943. doi: 10.3390/biomedicines10081943.
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.
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）获取大量脂质以实现快速生长，SREBP-1是一种主要的转录因子，可调节脂肪酸和胆固醇的合成以及胆固醇摄取。有趣的是，GBM细胞将大量脂质转移到脂滴（LDs）中，脂滴是中性脂质的特定储存细胞器，通过增加二酰甘油酰基转移酶1（DGAT1）和固醇-O-酰基转移酶1（SOAT1）的表达来防止脂毒性，这两种酶分别将过量的脂肪酸和胆固醇转化为三酰甘油和胆固醇酯。在这篇综述中，我们将总结我们对GBM中脂质代谢调节以促进肿瘤生长的理解的最新进展，并讨论通过破坏脂质储存特异性诱导肿瘤细胞脂毒性的新策略，这是一种有前景的治疗GBM的新途径。
