AUTHOR=Ichimura Yoshinobu , Komatsu Masaaki 

TITLE=Activation of p62/SQSTM1–Keap1–Nuclear Factor Erythroid 2-Related Factor 2 Pathway in Cancer

JOURNAL=Frontiers in Oncology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00210

DOI=10.3389/fonc.2018.00210

ISSN=2234-943X

ABSTRACT=<p>Autophagy and the Keap1–Nrf2 system are major cellular defense mechanisms against metabolic and oxidative stress. These two systems are linked <italic>via</italic> phosphorylation of the ubiquitin binding autophagy receptor protein p62/SQSTM1 in the p62–Keap1–Nrf2 pathway. The p62–Keap1–Nrf2 pathway plays a protective role in normal cells; however, recent studies indicate that this pathway induces tumorigenesis of pre-malignant cells, and promotes the growth and drug resistance of tumor cells <italic>via</italic> metabolic reprogramming mediated by Nrf2 activation. These findings suggest that impairment of autophagy is involved in the acquisition of malignancy and maintenance of tumors, and furthermore, that p62/SQSTM1 could be a potential target for chemotherapy in cancers that harbor excess p62.</p>