Thorne, JL and Campbell, MJ (2015) Nuclear Receptors and the Warburg effect in cancer. International Journal of Cancer, 137 (7). 1519 - 1527. ISSN 0020-7136
Abstract
In 1927 Otto Warburg established that tumours derive energy primarily from the conversion of glucose to lactic acid and only partially through cellular respiration involving oxygen. In the 1950’s he proposed that all causes of cancer reflected different mechanisms of disabling cellular respiration in favour of fermentation (now termed aerobic glycolysis). The role of aberrant glucose metabolism in cancer is now firmly established. The shift away from oxidative phosphorylation towards the metabolically expensive aerobic glycolysis is somewhat counter-intuitive given its wasteful nature. Multiple control processes are in place to maintain cellular efficiency and it is likely that these mechanisms are disrupted to facilitate the shift to the reliance on aerobic glycolysis. One such process of cell control is mediated by the nuclear receptor superfamily. This large family of transcription factors plays a significant role in sensing environmental cues and controlling decisions on proliferation, differentiation and cell death for example, to regulate glucose uptake and metabolism and to modulate the actions of oncogenes and tumour suppressors. In this review we highlight mechanisms by which nuclear receptors actions are altered during tumorigenic transformation and can serve to enhance the shift to aerobic glycolysis. At the simplest level, a basic alteration in NR behaviour can serve to enhance glycolytic flux thus providing a basis for enhanced survival within the tumour micro-environment. Ameliorating the enhanced NR activity in this context may help to sensitize cancer cells to Warburg targeted therapies and may provide future drug targets.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2014, The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Cancer; nuclear receptors; energy regulation; Warburg effect |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Sep 2015 11:06 |
Last Modified: | 22 Sep 2015 15:50 |
Published Version: | http://dx.doi.org/10.1002/ijc.29012 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/ijc.29012 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:89998 |