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癌细胞中 MYC 被抑制后的代谢变化。

Metabolic changes in cancer cells upon suppression of MYC.

机构信息

Department of Medicine, Feinberg School of Medicine, Northwestern University, 60611, Chicago, IL, USA.

出版信息

Cancer Metab. 2013 Feb 4;1(1):7. doi: 10.1186/2049-3002-1-7.

DOI:10.1186/2049-3002-1-7
PMID:24280108
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4178210/
Abstract

BACKGROUND

Cancer cells engage in aerobic glycolysis and glutaminolysis to fulfill their biosynthetic and energetic demands in part by activating MYC. Previous reports have characterized metabolic changes in proliferating cells upon MYC loss or gain of function. However, metabolic differences between MYC-dependent cancer cells and their isogenic differentiated counterparts have not been characterized upon MYC suppression in vitro.

RESULTS

Here we report metabolic changes between MYC-dependent mouse osteogenic sarcomas and differentiated osteoid cells induced upon MYC suppression. While osteogenic sarcoma cells increased oxygen consumption and spare respiratory capacity upon MYC suppression, they displayed minimal changes in glucose and glutamine consumption as well as their respective contribution to the citrate pool. However, glutamine significantly induced oxygen consumption in the presence of MYC which was dependent on aminotransferases. Furthermore, inhibition of aminotransferases selectively diminished cell proliferation and survival of osteogenic sarcoma MYC-expressing cells. There were minimal changes in ROS levels and cell death sensitivity to reactive oxygen species (ROS)-inducing agents between osteoid cells and osteogenic sarcoma cells. Nevertheless, the mitochondrial-targeted antioxidant Mito-Vitamin E still diminished proliferation of MYC-dependent osteogenic sarcoma cells.

CONCLUSION

These data highlight that aminotransferases and mitochondrial ROS might be attractive targets for cancer therapy in MYC-driven tumors.

摘要

背景

癌细胞通过激活 MYC 来部分满足其生物合成和能量需求，从而进行有氧糖酵解和谷氨酰胺分解。先前的研究已经描述了 MYC 功能丧失或获得时增殖细胞的代谢变化。然而，在体外抑制 MYC 时，尚未描述 MYC 依赖性癌细胞与其同基因分化对应物之间的代谢差异。

结果

在这里，我们报告了 MYC 抑制后依赖 MYC 的小鼠成骨肉瘤和分化成骨细胞之间的代谢变化。虽然成骨肉瘤细胞在 MYC 抑制后增加了耗氧量和备用呼吸能力，但它们在葡萄糖和谷氨酰胺消耗以及它们各自对柠檬酸池的贡献方面几乎没有变化。然而，在存在 MYC 的情况下，谷氨酰胺显著诱导了耗氧量，这依赖于转氨酶。此外，抑制转氨酶选择性地降低了表达 MYC 的成骨肉瘤细胞的增殖和存活。成骨细胞和成骨肉瘤细胞之间的 ROS 水平和对活性氧 (ROS) 诱导剂的细胞死亡敏感性没有明显变化。尽管如此，线粒体靶向抗氧化剂 Mito-Vitamin E 仍然降低了依赖 MYC 的成骨肉瘤细胞的增殖。

结论

这些数据强调了转氨酶和线粒体 ROS 可能是 MYC 驱动肿瘤癌症治疗的有吸引力的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/80b7ae9f6ccb/2049-3002-1-7-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/d288f22e6e1e/2049-3002-1-7-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/3fe0907b39fa/2049-3002-1-7-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/c755b9bc6829/2049-3002-1-7-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/a8bb745d582e/2049-3002-1-7-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/5b7eec282e6a/2049-3002-1-7-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/80b7ae9f6ccb/2049-3002-1-7-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/d288f22e6e1e/2049-3002-1-7-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/3fe0907b39fa/2049-3002-1-7-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/c755b9bc6829/2049-3002-1-7-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/a8bb745d582e/2049-3002-1-7-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/5b7eec282e6a/2049-3002-1-7-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e744/4178210/80b7ae9f6ccb/2049-3002-1-7-6.jpg

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