Oncogenic potential of Nrf2 and its principal target protein heme oxygenase-1

• Published in: Free radical biology & medicine Vol. 67; pp. 353 - 365
• Main Authors: Na, Hye-Kyung, Surh, Young-Joon
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2014
• Subjects: Adaptive survival response; Antineoplastic Agents - therapeutic use; Antioxidant response elements; Chemoresistance; Free radicals; Gamma Rays - therapeutic use; Gene Expression Regulation, Neoplastic; Heme oxygenase-1; Heme Oxygenase-1 - antagonists & inhibitors; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Humans; Molecular Targeted Therapy; Neoplasms - blood supply; Neoplasms - genetics; Neoplasms - pathology; Neoplasms - therapy; Neovascularization, Pathologic; NF-E2-Related Factor 2 - antagonists & inhibitors; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidative Stress; Photochemotherapy; Radiation-Sensitizing Agents - therapeutic use; Radioresistance; Redox balance; Signal Transduction; Tumor Microenvironment - drug effects; Tumor Microenvironment - radiation effects; Adaptive survival response; Free radicals; Nrf2; Heme oxygenase-1; Chemoresistance; Redox balance; Radioresistance; Antioxidant response elements
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2013.10.819

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential component of cellular defense against a vast variety of endogenous and exogenous insults, including oxidative stress. Nrf2 acts as a master switch in the circuits upregulating the expression of various stress-response proteins, especially heme oxygenase-1 (HO-1). Paradoxically, however, recent studies have demonstrated oncogenic functions of Nrf2 and its major target protein HO-1. Levels of Nrf2 and HO-1 are elevated in many different types of human malignancies, which may facilitate the remodeling of the tumor microenvironment making it advantageous for the autonomic growth of cancer cells, metastasis, angiogenesis, and tolerance to chemotherapeutic agents and radiation and photodynamic therapy. In this context, the cellular stress response or cytoprotective signaling mediated via the Nrf2–HO-1 axis is hijacked by cancer cells for their growth advantage and survival of anticancer treatment. Therefore, Nrf2 and HO-1 may represent potential therapeutic targets in the management of cancer. This review highlights the roles of Nrf2 and HO-1 in proliferation of cancer cells, their tolerance/resistance to anticancer treatments, and metastasis or angiogenesis in tumor progression. [Display omitted] •Active Nrf2 signaling could maintain a favorable redox balance in cancer cells.•Levels or activities of Nrf2 and HO-1 are abnormally elevated in various human malignancies.•Nrf2 and its target protein HO-1 may reflect the status of cancer progression.•Nrf2 and HO-1 may represent potential therapeutic targets in the management of cancer.