While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy.
While Nrf2 has been the topic of intensive research in cancer biology since its discovery in 1994, understanding the role of Nrf2 in cardiovascular disease has just begun.
We show that accumulation of the autophagy substrate p62/SQSTM1 in stressed Kras<sup>G12D</sup> acinar cells is associated with PDAC development and maintenance of malignancy in human cells and mice. p62 accumulation promotes neoplastic progression by controlling the NRF2-mediated induction of MDM2, which acts through p53-dependent and -independent mechanisms to abrogate checkpoints that prevent conversion of differentiated acinar cells to proliferative ductal progenitors.
We hope for the development of noninvasive biomarkers and novel therapeutic approaches for cancer based on Nrf2-directed cancer metabolic reprogramming in the near future.
We combined <i>in vitro</i> and <i>in vivo</i> methods to examine the effect of DMF on cancer cell death and the activation of the NRF2 antioxidant pathway.
Using a human mammary MCF7-derived AREc32 reporter cell line, we now report that all-trans retinoic acid (ATRA), and other retinoic acid receptor alpha (RARalpha) agonists, markedly reduces the ability of Nrf2 to mediate induction of ARE-driven genes by cancer chemopreventive agents including the metabolite of butylated hydroxyanisole, tert-butylhydroquinone (tBHQ).
Ultimately, defining and understanding the mechanisms responsible for NRF2 activation in cancer may lead to novel targets for therapeutic intervention.
Transcription factor Nrf2, which regulates the expression of cytoprotective and antioxidant enzymes, contributes to proliferation and resistance to chemotherapy in cancer.
To examine the regulatory crosstalk between the transcription factors Nrf2 and AP-1 in prostate cancer (PCa) by dietary cancer chemopreventive compounds (-)epigallocatechin-3-gallate (EGCG) from green tea and sulforaphane (SFN) from cruciferous vegetables.
This study reveals a previously unappreciated role for Nrf2 in the regulation of autophagy and the innate antiviral response that complements the therapeutic potential of VSV-directed oncolysis against multiple types of OV-resistant or chemoresistant cancer.
This set of NRF2 "cancer target genes" includes canonical redox-related NRF2 targets, as well as target genes that have not been previously linked to NRF2 activation.
This review provides an overview of (1) the Nrf2-Keap1 signaling pathway, (2) the dual role of Nrf2 in cancer, (3) the molecular basis of Nrf2 activation in cancer cells, and (4) the challenges in the development of Nrf2-based drugs for chemoprevention and chemotherapy.
This review aims to rationalize the existing functions of Nrf2 in chemoprevention and tumorigenesis, as well as the somatic mutations of Nrf2 and Keap1 in cancer and Nrf2 cross talk with miRNAs.
These emerging molecular mechanisms and the therapeutic perspective of targeting Nrf2-p62 interaction in HCC are discussed in this paper along with the prognostic value of autophagy in this type of cancer.