文章：

为什么癌症有高有氧糖酵解？

Why do cancers have high aerobic glycolysis?

原文发布日期：2004-11-01

DOI: 10.1038/nrc1478

类型: Review Article

开放获取: 否

要点：

1. Widespread clinical use of ¹⁸fluorodeoxyglucose positron-emission tomography has demonstrated that the glycolytic phenotype is observed in most human cancers.
2. The concept of carcinogenesis as a process that occurs by somatic evolution clearly implies that common traits of the malignant phenotype, such as upregulation of glycolysis, are the result of active selection processes and must confer a significant, identifiable growth advantage.
3. Constitutive upregulation of glycolysis is likely to be an adaptation to hypoxia that develops as pre-malignant lesions grow progressively further from their blood supply. At this stage, the blood supply remains physically separated from the growing cells by an intact basement membrane.
4. Increased acid production from upregulation of glycolysis results in microenvironmental acidosis and requires further adaptation through somatic evolution to phenotypes resistant to acid-induced toxicity.
5. Cell populations that emerge from this evolutionary sequence have a powerful growth advantage, as they alter their environment through increased glycolysis in a way that is toxic to other phenotypes, but harmless to themselves. The environmental acidosis also facilitates invasion through destruction of adjacent normal populations, degradation of the extracellular matrix and promotion of angiogenesis.
6. We propose that the glycolytic phenotype, by conferring a powerful growth advantage, is necessary for evolution of invasive human cancers.

要点翻译：

1. 18氟脱氧葡萄糖正电子发射断层扫描的广泛应用证实，糖酵解表型在大多数人类癌症中存在。
2. 致癌作用作为体细胞进化过程的概念明确提示，恶性表型的常见特征（如糖酵解上调）是主动选择过程的结果，必然赋予肿瘤显著且可识别的生长优势。
3. 糖酵解的持续性上调可能是对缺氧环境的适应，这种缺氧随着癌前病变逐渐远离血液供应而发展。在此阶段，完整的基底膜仍将血液供应与生长中的细胞物理隔离。
4. 糖酵解上调导致的酸产量增加会引起微环境酸中毒，需要通过体细胞进化进一步适应，形成耐酸诱导毒性的表型。
5. 经历这一进化序列的细胞群体获得强大的生长优势，因为它们通过增强糖酵解改变微环境，这种改变对其他表型具有毒性，但对自身无害。环境酸中毒还通过破坏邻近正常细胞群、降解细胞外基质和促进血管生成，为侵袭提供便利。
6. 我们认为，糖酵解表型通过赋予肿瘤强大的生长优势，成为人类浸润性癌症进化过程中的必要因素。

英文摘要：

If carcinogenesis occurs by somatic evolution, then common components of the cancer phenotype result from active selection and must, therefore, confer a significant growth advantage. A near-universal property of primary and metastatic cancers is upregulation of glycolysis, resulting in increased glucose consumption, which can be observed with clinical tumour imaging. We propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions. However, upregulation of glycolysis leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity. Subsequent cell populations with upregulated glycolysis and acid resistance have a powerful growth advantage, which promotes unconstrained proliferation and invasion.

摘要翻译： 

如果癌症的发生是通过体细胞进化实现的，那么癌症表型的共同组分就是主动选择的结果，因此必须带来显著的生长优势。原发性和转移性癌症几乎普遍存在糖酵解上调，导致葡萄糖消耗增加，可通过临床肿瘤成像观察到。我们认为，即使在有氧条件下仍持续将葡萄糖代谢为乳酸，是对癌前病变中间歇性缺氧的一种适应。然而，糖酵解上调会导致微环境酸化，从而促使细胞进化出对酸诱导毒性的抵抗表型。随后，兼具糖酵解上调和耐酸性的细胞群体获得强大的生长优势，推动其不受限制的增殖与侵袭。

原文链接：

Why do cancers have high aerobic glycolysis?