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Published Online: 23 October 2018

The Regulation of NRF2 by Nutrient-Responsive Signaling and Its Role in Anabolic Cancer Metabolism

Publication: Antioxidants & Redox Signaling
Volume 29, Issue Number 17

Abstract

Significance: The stress responsive transcription factor nuclear factor erythroid 2 p45-related factor 2, or NRF2, regulates the expression of many cytoprotective enzymes to mitigate oxidative stress under physiological conditions. NRF2 is activated in response to oxidative stress, growth factor signaling, and changes in nutrient status. In addition, somatic mutations that disrupt the interaction between NRF2 and its negative regulator Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated 1 (KEAP1) commonly occur in cancer and are thought to promote tumorigenesis.
Recent Advances: While it is well established that aberrant NRF2 activation results in enhanced antioxidant capacity in cancer cells, recent exciting findings demonstrate a role for NRF2-mediated metabolic deregulation that supports cancer cell proliferation.
Critical Issues: In this review, we describe how the NRF2-KEAP1 signaling pathway is altered in cancer, how NRF2 is regulated by changes in cellular metabolism, and how NRF2 reprograms cellular metabolism to support proliferation.
Future Directions: Future studies will delineate the NRF2-regulated processes critical for metabolic adaptation to nutrient availability, cellular proliferation, and tumorigenesis. Antioxid. Redox Signal. 00, 000–000.

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cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 29Issue Number 17December 10, 2018
Pages: 1774 - 1791
PubMed: 28899208

History

Published in print: December 10, 2018
Published online: 23 October 2018
Published ahead of print: 16 October 2017
Published ahead of production: 13 September 2017
Accepted: 12 September 2017
Received: 5 September 2017

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Sae Bom Lee*
Department of Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida.
Brianna N. Sellers*
Department of Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida.
Gina M. DeNicola [email protected]
Department of Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, Florida.

Notes

*
These authors contributed equally to this work.
Address correspondence to: Dr. Gina M. DeNicola, Department of Cancer Imaging and Metabolism, Moffitt Cancer Center and Research Institute, Tampa, FL 33612 [email protected]

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