小柯机器人

美国斯坦福大学的Dean W. Felsher、Richard N. Zare与宾夕法尼亚大学的Chi V. Dang等研究人员合作发现，原癌基因MYC与SERBP蛋白共同调节肿瘤生长所必需的脂肪生成。相关论文于2019年8月22日在线发表在《细胞—代谢》上。

研究人员发现，原癌基因MYC与转录因子SREBP1（sterol-regulated element-binding protein）共同调节脂肪生成以促进肿瘤发生。通过使用人和小鼠肿瘤来源的细胞系、肿瘤异种移植物和四种条件转基因小鼠模型（由MYC引发肿瘤），研究人员发现，MYC调节脂肪生成基因、酶和代谢物。研究人员发现MYC诱导SREBP1，然后二者共同激活脂肪酸（FA）合成并利用葡萄糖和谷氨酰胺促进FA链延伸。

此外，通过采用解吸电喷雾电离质谱成像（DESI-MSI），研究人员观察到MYC在不同癌症诱导后的体内脂质组学变化，例如，甘油磷酸甘油的全面增加。抑制FA合成后，肿瘤的发生被阻断，肿瘤在异种移植和原代转基因小鼠模型中均缩小，这些结果揭示了MYC诱导的肿瘤对脂肪生成抑制的脆弱性。

据了解，癌症中的脂质代谢经常受到扰动，但其潜在机制尚不清楚。

附：英文原文

Title: The MYC Oncogene Cooperates with Sterol-Regulated Element-Binding Protein to Regulate Lipogenesis Essential for Neoplastic Growth

Author: Arvin M. Gouw,Katherine Margulis,Natalie S. Liu,Sudha J. Raman,Anthony Mancuso,Georgia G. Toal,Ling Tong,Adriane Mosley,Annie L. Hsieh,Delaney K. Sullivan,Zachary E. Stine,Brian J. Altman,Almut Schulze,Chi V. Dang,Richard N. Zare,Dean W. Felsher

Issue&Volume: 22 August 2019

Abstract: Lipid metabolism is frequently perturbed in cancers, but the underlying mechanism is unclear. We present comprehensive evidence that oncogene MYC, in collaboration with transcription factor sterol-regulated element-binding protein (SREBP1), regulates lipogenesis to promote tumorigenesis. We used human and mouse tumor-derived cell lines, tumor xenografts, and four conditional transgenic mouse models of MYC-induced tumors to show that MYC regulates lipogenesis genes, enzymes, and metabolites. We found that MYC induces SREBP1, and they collaborate to activate fatty acid (FA) synthesis and drive FA chain elongation from glucose and glutamine. Further, by employing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we observed in vivo lipidomic changes upon MYC induction across different cancers, for example, a global increase in glycerophosphoglycerols. After inhibition of FA synthesis, tumorigenesis was blocked, and tumors regressed in both xenograft and primary transgenic mouse models, revealing the vulnerability of MYC-induced tumors to the inhibition of lipogenesis.

DOI: https://doi.org/10.1016/j.cmet.2019.07.012

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30385-7#

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