The Warburg effect: Essential part of metabolic reprogramming and central contributor to cancer progression.

CONCLUSIONS: There is clear evidence that mitochondria are not defective in most cancers. Aerobic glycolysis, a key metabolic feature of the Warburg phenotype, is caused by active metabolic reprogramming required to support sustained cancer cell proliferation and malignant progression. This metabolic switch is directed by altered growth factor signaling, hypoxic or normoxic activation of HIF-1α- transcription, oncogene activation or loss-of-function of suppressor genes, and is implemented in the hostile tumor microenvironment. The "selfish" reprogramming includes (a) overexpression of glucose transporters and of key glycolytic enzymes, and an accelerated glycolytic flux with subsequent accumulation and diversion of glycolytic intermediates for cancer biomass synthesis, (b) high-speed ATP production that meets the energy demand, and (c) accumulation of lactate which drives tumor progression and largely contributes to tumor acidosis, which in turn synergistically favors tumor progression and resistance to certain antitumor therapies, and compromises anti-tumor immunity. In all, the Warburg effect is the central contributor to the cancer progression machinery. PMID: 30822194 [PubMed - as supplied by publisher]
Source: International Journal of Radiation Biology - Category: Radiology Tags: Int J Radiat Biol Source Type: research