Na Hye-Kyung, Surh Young-Joon
Department of Food & Nutrition, College of Human Ecology, Sungshin Women's University, Seoul 142-732, South Korea.
Tumor Microenvironment Global Core Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea; Department of Molecular Medicine and Biopharmaceutical Science, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, South Korea; Cancer Research Institute, Seoul National University, Seoul 110-744, South Korea.
Free Radic Biol Med. 2014 Feb;67:353-65. doi: 10.1016/j.freeradbiomed.2013.10.819. Epub 2013 Nov 5.
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.
核因子红细胞2相关因子2（Nrf2）是细胞抵御多种内源性和外源性损伤（包括氧化应激）的重要组成部分。Nrf2在上调各种应激反应蛋白（尤其是血红素加氧酶-1，HO-1）表达的信号通路中起主控开关的作用。然而，矛盾的是，最近的研究表明Nrf2及其主要靶蛋白HO-1具有致癌功能。在许多不同类型的人类恶性肿瘤中，Nrf2和HO-1的水平都会升高，这可能会促进肿瘤微环境的重塑，从而有利于癌细胞的自主生长、转移、血管生成以及对化疗药物、放疗和光动力疗法的耐受性。在这种情况下，通过Nrf2-HO-1轴介导的细胞应激反应或细胞保护信号被癌细胞利用，以获得生长优势和对抗癌治疗的耐受性。因此，Nrf2和HO-1可能是癌症治疗中的潜在靶点。本综述重点介绍了Nrf2和HO-1在癌细胞增殖、对抗癌治疗的耐受性/抗性以及肿瘤进展中的转移或血管生成方面的作用。
