Is cancer a disease of abnormal cellular metabolism? New angles on an old idea.
Is cancer a disease of abnormal cellular metabolism? New angles on an old idea.
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DOI：
10.1097/gim.0b013e31818b0d9b
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发表时间：
2008-11
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影响因子：
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通讯作者：
DeBerardinis RJ
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作者：
DeBerardinis RJ
20世纪20年代，Otto Warburg观察到肿瘤细胞消耗大量葡萄糖，远多于正常细胞，并将其中大部分转化为乳酸。这种现象现在被称为“瓦尔堡效应”，是癌症最早的一般概念之一的基础：细胞代谢活动的根本紊乱是肿瘤形成和生长的根源。在接下来的几十年里，随着人们越来越明显地发现染色体异常以及最终单个基因导致癌症，癌症的“代谢”模型失去了很大的吸引力，尽管新兴技术正在临床上利用瓦尔堡效应来检测体内肿瘤。我们现在知道肿瘤抑制基因和原癌基因影响新陈代谢，并且这些基因的突变可以促进支持细胞生长和增殖的代谢表型。因此，这些进展统一了癌症代谢和遗传模型的各个方面，并激发了人们对细胞代谢在肿瘤发生中的作用的新兴趣。这篇综述重新评估了细胞代谢失调是癌症的一个关键特征这一观点，并讨论了一些多年来一直没有受到关注、现在值得更密切关注的代谢问题。
In the 1920s, Otto Warburg observed that tumor cells consume a large amount of glucose, much more than normal cells, and convert most of it to lactic acid. This phenomenon, now known as the ‘Warburg effect,’ is the foundation of one of the earliest general concepts of cancer: that a fundamental disturbance of cellular metabolic activity is at the root of tumor formation and growth. In the ensuing decades, as it became apparent that abnormalities in chromosomes and eventually individual genes caused cancer, the ‘metabolic’ model of cancer lost a good deal of its appeal, even as emerging technologies were exploiting the Warburg effect clinically to detect tumors in vivo. We now know that tumor suppressors and proto-oncogenes influence metabolism, and that mutations in these genes can promote a metabolic phenotype supporting cell growth and proliferation. Thus, these advances have unified aspects of the metabolic and genetic models of cancer, and have stimulated a renewed interest in the role of cellular metabolism in tumorigenesis. This review reappraises the notion that dysregulated cellular metabolism is a key feature of cancer, and discusses some metabolic issues that have escaped scrutiny over the years and now deserve closer attention.