Xiong Bin, Zhang Yang, Liu Siyi, Liao Shan, Zhou Zihua, He Qian, Zhou Yanhong
Department of Radiation Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.
Cancer Research Institute, Basic School of Medicine, Central South University, Changsha, Hunan, China.
FASEB J. 2025 Apr 30;39(8):e70565. doi: 10.1096/fj.202500238RRR.
Cancer cells are capable of surviving, proliferating, and invading or migrating within hypoxic environments by regulating various adaptive mechanisms. Due to the activation of oncogenes and the inactivation of tumor suppressor genes, and relative deficiencies in oxygen and nutrients, cancer cells demonstrate elevated production of reactive oxygen species (ROS), primarily sourced from NADPH oxidases (NOX family). A key aspect of the reorientation of tumor cell metabolism is the combating of cellular oxidative stress through the promotion of antioxidant molecule synthesis to counteract ROS production. Given that most cancers experience hypoxia and that NOX is closely linked to numerous redox-dependent signaling pathways, the expression and function of NOX are altered in various malignancies. Therefore, this review summarizes the characteristics of NOX family members, their influence on tumor proliferation, invasion, and migration, the role of NOX in promoting tumor angiogenesis, the impact of NOX on the function of immune cells within the tumor microenvironment, and the potential of targeting NOX in tumor therapy. This aims to offer a fresh viewpoint on a comprehensive understanding of the functions of NOX family members.
癌细胞能够通过调节各种适应性机制在缺氧环境中存活、增殖、侵袭或迁移。由于癌基因的激活和肿瘤抑制基因的失活,以及氧气和营养物质的相对缺乏,癌细胞表现出活性氧(ROS)产生增加,主要来源于烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX家族)。肿瘤细胞代谢重新定向的一个关键方面是通过促进抗氧化分子合成来对抗ROS产生,从而对抗细胞氧化应激。鉴于大多数癌症都经历缺氧,且NOX与众多氧化还原依赖性信号通路密切相关,NOX的表达和功能在各种恶性肿瘤中都会发生改变。因此,本综述总结了NOX家族成员的特征、它们对肿瘤增殖、侵袭和迁移的影响、NOX在促进肿瘤血管生成中的作用、NOX对肿瘤微环境中免疫细胞功能的影响,以及在肿瘤治疗中靶向NOX的潜力。这旨在为全面理解NOX家族成员的功能提供一个新的视角。