Mao Hongmei, Zhao Xiaocui, Sun Shao-Cong
Institute for Immunology, Chinese Institutes for Medical Research, Beijing, China.
School of Basic Medicine, Capital Medical University, Beijing, China.
Cell Mol Immunol. 2025 Jun 25. doi: 10.1038/s41423-025-01310-w.
Nuclear factor-κB (NF-κB) is a family of transcription factors that transactivates genes associated with a wide range of biological processes, including immune responses, inflammation, cell growth and survival. Dysregulated NF-κB activation contributes to acute and chronic inflammatory disorders, mostly through the aberrant induction of genes encoding proinflammatory factors and metabolic disorders. Abnormal NF-κB activation also influences the development and stability of regulatory T cells, contributing to the pathogenesis of autoimmune disorders. Given the critical role of inflammation in promoting oncogenesis, the proinflammatory role of NF-κB is also linked to cancer development. In addition, aberrant NF-κB activation contributes to uncontrolled tumor cell proliferation, survival, metabolism, metastasis, tumor angiogenesis and therapy resistance. These pathological functions of NF-κB highlight its potential as a therapeutic target for both inflammatory diseases and cancer. In this review, we summarize recent findings regarding the role of NF-κB in these pathological processes and discuss the underlying mechanisms. We also explore potential therapeutic strategies aimed at targeting the NF-κB pathway for disease treatment, along with an analysis of possible challenges.
核因子-κB（NF-κB）是一类转录因子家族，可反式激活与多种生物学过程相关的基因，包括免疫反应、炎症、细胞生长和存活。NF-κB激活失调会导致急性和慢性炎症性疾病，主要是通过异常诱导编码促炎因子的基因和代谢紊乱。异常的NF-κB激活还会影响调节性T细胞的发育和稳定性，从而导致自身免疫性疾病的发病机制。鉴于炎症在促进肿瘤发生中的关键作用，NF-κB的促炎作用也与癌症发展有关。此外，异常的NF-κB激活会导致肿瘤细胞不受控制的增殖、存活、代谢、转移、肿瘤血管生成和治疗抵抗。NF-κB的这些病理功能突出了其作为炎症性疾病和癌症治疗靶点的潜力。在这篇综述中，我们总结了关于NF-κB在这些病理过程中作用的最新发现，并讨论了潜在机制。我们还探讨了针对NF-κB途径进行疾病治疗的潜在策略，以及对可能挑战的分析。
