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Nuclear factor kappa B (NF-κB) transcription factors are evolutionarily conserved, coordinating regulators of immune and inflammatory responses. They also play a pivotal role in oncogenesis and metabolic disorders. Several studies during the past two decades have highlighted the key role of the IKK/NF-κB pathway in the induction and maintenance of the state of inflammation that underlies metabolic diseases such as obesity and type 2 diabetes. Recent reports, however, reveal an even more intimate 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 beyond metabolic diseases, including cancer, ageing and anticancer therapy. In this review, we discuss these emerging bioenergetic functions of NF-κB and their significance to oncogenesis. [ABSTRACT FROM AUTHOR]

Cell proliferation is a metabolically demanding process. It requires active reprogramming of cellular bioenergetic pathways towards glucose metabolism to support anabolic growth. NF-?B/Rel transcription factors coordinate many of the signals that drive proliferation during immunity, inflammation and oncogenesis, but whether NF-?B regulates the metabolic reprogramming required for cell division during these processes is unknown. Here, we report that NF-?B organizes energy metabolism networks by controlling the balance between the utilization of glycolysis and mitochondrial respiration. NF-?B inhibition causes cellular reprogramming to aerobic glycolysis under basal conditions and induces necrosis on glucose starvation. The metabolic reorganization that results from NF-?B inhibition overcomes the requirement for tumour suppressor mutation in oncogenic transformation and impairs metabolic adaptation in cancer in vivo. This NF-?B-dependent metabolic pathway involves stimulation of oxidative phosphorylation through upregulation of mitochondrial synthesis of cytochrome c oxidase 2 (SCO2; ref. ). Our findings identify NF-?B as a physiological regulator of mitochondrial respiration and establish a role for NF-?B in metabolic adaptation in normal cells and cancer. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]