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Review
. 2017 Jun 13:4:306-318.
doi: 10.1016/j.toxrep.2017.06.002. eCollection 2017.

Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy

Priyanka Basak  1 , Pritam Sadhukhan  1 , Poulami Sarkar  1 , Parames C Sil  1
Affiliations
Review

Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy

Priyanka Basak et al. Toxicol Rep. .

Abstract

The Nuclear factor erythroid2-related factor2 (Nrf2), a master regulator of redox homoeostasis, is a key transcription factor regulating a wide array of genes for antioxidant and detoxification enzymes. It protects organs from various kinds of toxic insults. On the other hand, activation of Nrf2 is also correlated with cancer progression and chemoresistance. Downregulation of Nrf2 activity has attracted an increasing amount of attention as it may provide an alternative cancer therapy. In this review, we examine recent studies on roles of Nrf2 in several pathophysiological conditions emphasising cancer. We discuss elaborately the current knowledge on Nrf2 regulation including KEAP1-dependent and KEAP1-independent cascades. KEAP1/Nrf2 system is a master regulator of cellular response against a variety of environmental stresses. We also highlight several tightly controlled regulations of Nrf2 by numerous proteins, small molecules, toxic metals, etc. In addition, we evaluate the possible therapeutic approaches of increasing chemosensitivity via modulating Nrf2 signaling.

Keywords: Carcinogenesis; Cell proliferation; Chemoprevention; KEAP1; Nrf2; Oxidative stress; Transcription factor.

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Figures

Fig. 1
Fig. 1
The structure of Nrf2 containing seven domains.
Fig. 2
Fig. 2
Regulations of Nrf2 by several factors. The green colour indicates upregulation of Nrf2 activity and the red colour indicates downregulation of Nrf2 activity.
Fig. 3
Fig. 3
Activation and mechanism of action of Nrf2. During normal condition, Nrf2 is sequestered in the cytoplasm by KEAP1. Any kind of stress leads to degradation of KEAP1 and Nrf2 mediated transcriptional upregulation.
Fig. 4
Fig. 4
Functions of Nrf2. Nrf2 maintains homeostasis in the body. It plays a beneficial role in several diseased conditions, but during cancer, it plays a detrimental role in promoting cancer progression.
Fig. 5
Fig. 5
Schematic representation of the dual role of Nrf2 in cancer progression and therapy.
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