Section of Inflammation and Signal Transduction, Department of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Int J Biochem Cell Biol. 2012 Dec;44(12):2238-43. doi: 10.1016/j.biocel.2012.08.002. Epub 2012 Aug 10.
NF-κB transcription factors are evolutionarily conserved, central coordinators of immune and inflammatory responses. They also play a pivotal role in oncogenesis. NF-κB exerts these functions by regulating the transcription of genes encoding many immunoregulators, inflammatory mediators and inhibitors of apoptosis. Several studies during the past few years have also underscored the key role of the IKK/NF-κB pathway in the induction and maintenance of the state of inflammation that underlies metabolic pathologies such as obesity, insulin resistance and type-2 diabetes, reflecting the co-evolution and integration of nutrient- and pathogen-sensing systems. Recent reports, however, are revealing an even more intimate, direct connection between NF-κB and metabolism. These studies demonstrate that NF-κB regulates energy homeostasis via direct engagement of the cellular networks governing glycolysis and respiration, with profound implications that extend beyond metabolic pathologies, to cellular physiology, cancer, and anti-cancer therapy. In this review article, we discuss these emerging metabolic functions of NF-κB and their significance to oncogenesis and cancer treatment.
NF-κB 转录因子是进化上保守的、免疫和炎症反应的核心协调因子。它们在肿瘤发生中也起着关键作用。NF-κB 通过调节编码许多免疫调节剂、炎症介质和细胞凋亡抑制剂的基因的转录来发挥这些功能。过去几年的几项研究也强调了 IKK/NF-κB 途径在诱导和维持肥胖、胰岛素抵抗和 2 型糖尿病等代谢病理学中炎症状态方面的关键作用，反映了营养和病原体感应系统的共同进化和整合。然而，最近的报告揭示了 NF-κB 与代谢之间更密切、更直接的联系。这些研究表明，NF-κB 通过直接参与调节糖酵解和呼吸的细胞网络来调节能量稳态，这具有深远的意义，不仅限于代谢病理学，还包括细胞生理学、癌症和抗癌治疗。在这篇综述文章中，我们讨论了 NF-κB 的这些新兴代谢功能及其对肿瘤发生和癌症治疗的意义。
