Dissecting the Crosstalk between NRF2 Signaling and Metabolic Processes in Cancer
Department of Cancer Physiology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA
Cancer Biology PhD Program, University of South Florida, Tampa, FL 33612, USA
Author to whom correspondence should be addressed.
Received: 24 September 2020 / Revised: 14 October 2020 / Accepted: 15 October 2020 / Published: 17 October 2020
The stress-responsive transcription factor NRF2 (nuclear factor-erythroid 2 p45-related factor 2) directs cellular metabolic processes that can have diverse effects in the context of cancer. This review addresses how NRF2 and its negative regulator KEAP1 (Kelch-like ECH-associated protein 1) collectively modulate and respond to metabolism. We highlight NRF2-regulated processes relevant to the antioxidant system, cellular proliferation, and survival, including metabolism of amino acids, lipids, NADPH (reduced nicotinamide adenine dinucleotide phosphate), iron, and heme. We also review the stabilization of NRF2 by electrophiles, metabolites, and autophagy. Finally, we discuss topics that warrant further investigation into the KEAP1/NRF2 pathway’s role in tumor progression.