Two Faces of Nrf2 in Cancer

Nuclear factor erythroid 2–related factor 2 (Nrf2) serves as a “main regulator” in response to internal or external cell stressors through coordinated induction of a wide range of cytoprotective genes. In cancer cells, Nrf2 increases expression of cytoprotective genes and, as a result, promotes proliferation through inhibition of apoptosis and metabolic reprogramming. Therefore, the activation of Nrf2 is an important regulator for prevention of cancer triggered by stresses and toxins. Defense system is activated by cellular pathways to ensure that response to stresses and toxins is sufficient for needs of the body. Nrf2 is a regulator of genes mediated by antioxidant response elements. Nrf2 is a pleiotropic gene that represents highly researched strategy in cancers. During recent decades, emerging evidence shows that Nrf2 is generally activated in many types of cancer by many mechanisms. Nrf2 has been showed to contribute to chemoresistance of cancer cells, as well as carcinogenesis due to inflammation, in recent studies. This review provides an overview of current mechanisms of regulation of Nrf2 in normal cells and its dual effects in cancer. This chapter aims to rationalize these double roles by criticizing dependence of Nrf2 functions and methods behind these contradictory data