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Cited by 893

The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.

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

Vaupel, Peter, Schmidberger, Heinz, Mayer, Arnulf·2019·International Journal of Radiation Biology
DOI 10.1080/09553002.2019.1589653
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Abstract

In the early 1920s, Warburg published experimental data on the enhanced conversion of glucose to pyruvate (followed by lactate formation) even in the presence of abundant oxygen (aerobic glycolysis, Warburg effect). He attributed this metabolic trait to a respiratory injury and considered this a universal metabolic alteration in carcinogenesis. This interpretation of the data was questioned since the early 1950s. Realistic causative mechanisms and consequences of the Warburg effect were described only during the past 15 years and are summarized in this article. 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 antitumor immunity. Altogether, the Warburg effect is the central contributor to the cancer progression machinery.

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Metadata

Authors
Vaupel, P., Schmidberger, H., & Mayer, A.
Venue
International Journal of Radiation Biology
Publisher
Informa UK Limited
Published
2019-03-22
Volume
95
Issue
7
Pages
912-919
ISSN
  • 0955-3002 (ISSN-L)
  • 1362-3095
DOI
10.1080/09553002.2019.1589653
OpenAlex
W2918298756
Cited by
893
References
71
FWCI
22.46
Type
journal article
Language
en
Open access
closed

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