Why do cancers have high aerobic glycolysis?

RA Gatenby, RJ Gillies - Nature reviews cancer, 2004 - nature.com
RA Gatenby, RJ Gillies
Nature reviews cancer, 2004nature.com
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 …
Abstract
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.
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